bluuebunny/crossref_metadata_2025 huggingface dataset:
Trisomy 7p resulting from isochromosome formation and whole‐arm translocation
Authors: Lurie Iosif W. , Schwartz Marcia F. , Schwartz Stuart , Cohen Maimon M.
Published: June 2005

A newborn boy with a large anterior fontanel, minor facial anomalies, postaxial polydactyly, patent ductus arteriosus, and developmental delay had trisomy of 7p due to an i(7p) and a concomitant t(2;7) (q37.3; q11.1). Significant enlargement of the fontanel is the most characteristic finding in most patients with duplications involving 7p15‐pter. Asynchrony in fore‐ and hindbrain and hemisphere formation leading to brain asymmetry and various defects in the posterior fossa are typical of infants with duplications of 7p11‐p12. A variety of heart defects has also been found in more than 50% of patients with duplication of 7p segments.

Isochromosome formation accompanied by whole‐arm translocation, resulting in uniparental isodisomy for the involved segment, is an extremely rare cause leading to partial trisomies. Although it is not clear whether isochromosome formation precedes the whole‐arm translocation or follows it, the secondary rearrangement may have adaptive significance. © 1995 Wiley‐Liss, Inc.
Waardenburg syndrome type II: Phenotypic findings and diagnostic criteria
Authors: Liu Xue‐Zhong , Newton Valerie E. , Read Andrew P.
Published: June 2005

The Waardenburg syndrome (WS) consists of at least two distinct autosomal dominant hereditary disorders. WS Type I has been mapped to the distal part of chromosome 2q and the gene identified as PAX3. Other gene(s) are responsible for WS Type II. Mapping WS Type II requires accurate diagnosis within affected families. To establish diagnostic criteria for WS Type II, 81 individuals from 21 families with Type II WS were personally studied, and compared with 60 personally studied patients from 8 families with Type I and 253 cases of WS (Type I or II) from the literature.

Sensorineural hearing loss (77%) and heterochromia iridum (47%) were the two most important diagnostic indicators for WS Type II. Both were more common in Type II than in Type I. Other clinical manifestations, such as white forelock and skin patches, were more frequent in Type I. We estimate the frequency of phenotypic traits and propose diagnostic criteria for WS Type II. In practice, a diagnosis of WS Type II can be made with confidence given a family history of congenital hearing loss and pigmentary disorders, where individuals have been accurately measured for ocular distances to exclude dystopia canthorum. © 1995 Wiley‐Liss, Inc.
Syndrome of proximal interstitial deletion 4p15: Report of three cases and review of the literature
Authors: Chitayat David , Ruvalcaba Rogelio H. A. , Babul Riyana , Teshima Ikuko E. , Posnick Jeffrey C. , Vekemans Michel J. J. , Scarpelli Helene , Thuline Horace
Published: June 2005

We report on two boys and a girl with interstitial deletion in the short arm of chromosome 4 including the segment p15.2p15.33. All had normal growth with psychomotor retardation, multiple minor congenital anomalies, and a characteristic face distinct from that of the Wolf‐Hirschhorn syndrome. One of the patients had congenitally enlarged penis. These patients resemble some of the previously reported patients with similar cytogenetic abnormalities and suggests the recognition of a specific clinical chromosome deletion syndrome. © 1995 Wiley‐Liss, Inc.
Nutritional patterns of mothers of children with neural tube defects in Newfoundland
Authors: Friel James K. , Frecker Maxine , Fraser F. Clarke
Published: June 2005

In an exploratory study of the genetic epidemiology of neural tube defects in Newfoundland, we studied mothers who had given birth to a child with a neural tube defect (NTD) with respect to their nutrition, as well as various other factors. The frequency of NTD in the area studied was 3.5/1,000 births and has not decreased recently, as it has in some other parts of the world.

Twenty‐five mothers of children with NTD and a comparison group (CG), matched for age and neighbourhood, completed 3 day dietary records. The NTD group consisted of all mothers who had given birth to an NTD child within the previous 3.5 years in the chosen area. The CG mothers were ascertained through the local public health nurse who chose the nearest unaffected child born in the same time period as the NTD probands.

NTD mothers were younger, heavier, and of lower socioeconomic status than were CG mothers. CG group women consumed more vitamin supplements during the periconceptional period (P<0.05) and consumed more dairy and cereal products, fruits and vegetables (other than potatoes), and fewer sweets than did NTD mothers. Sixty‐four percent of NTD mothers had folacin intakes below the recommended level (168 mg) compared to 27% of CG mothers (P<0.01).

These findings support previous evidence that poor maternal nutrition, and low dietary folate in particular, increase the chance of having a child with an NTD, and emphasize the need for supplementary folate in the diet of women of childbearing age in areas where the frequency of NTDs is high. © 1995 Wiley‐Liss, Inc.
Dominant mesomelic shortness of stature with acral synostoses, umbilical anomalies, and soft palate agenesis
Authors: Verloes Alain , David Albert
Published: June 2005

We report on a father and 2 children (a living 4‐year‐old girl and an aborted 18‐week‐old fetus) with a dominantly inherited form of mesomelic shortness of stature with severe ankle, knee, and elbow involvement. Skeletal abnormalities included brachymetacarpy and brachymetatarsy of the 3rd to 5th rays, synostoses in these bones, synostoses of metacarpals and metatarsals II to V with the corresponding carpal/tarsal bones, partial fusion in the proximal row of carpal bones, and mild vertebral anomalies. Father and daughter also had downslanted palpebral fissures, beaked nose, hypertelorism, ptosis, microretrognathia, and transverse agenesis of the soft palate. Abnormally short umbilical cord with unusually long skin coverage was present. Mesomelic shortness worsens with time, with progressive curvature of the forearm. This condition appears to represent a previously undescribed MCA/dysostosis syndrome. © 1995 Wiley‐Liss, Inc.
Distal aphalangia, syndactyly, and extra metatarsal, associated with short stature, microcephaly, and borderline intelligence: A new autosomal dominant disorder
Authors: Martínez‐Frías M. L. , Martín M. , Pardo M. , de Las Heras F. Fernandez , Frías J. L.
Published: June 2005

We report on 3 members of a Spanish family with partial aphalangia, syndactyly with duplication of metatarsal IV, microcephaly, dull intelligence, and short stature. The MCA pattern observed in this family appears to constitute a previously underscribed syndrome. © 1995 Wiley‐Liss, Inc.
Skeletal manifestations in Fryns syndrome
Authors: Tsukahara Masato , Sase Masakatsu , Tateishi Hiroshi , Saito Tsuyoshi , Kato Hiroshi , Furukawa Susumu
Published: June 2005

We report on a female baby with Fryns syndrome who died soon after birth. The patient had short limbs, coarse face, hypoplastic lungs, diaphragmatic hernia, and acral hypoplasia. Literature review disclosed varying degrees of skeletal manifestations in Fryns syndrome; short limbs may be a component of Fryns syndrome. © 1995 Wiley‐Liss, Inc.
Developmental anomalies suggestive of the human homologue of the mouse mutant disorganization
Authors: Elliott Alison M. , Chen Moy‐Fong , Azouz E. Michel , Teebi Ahmad S.
Published: June 2005

We describe a 21‐week‐old fetus with a pattern of multiple congenital anomalies suggestive of the human homologue of the mouse mutant disorganization (Ds). Manifestations included facial asymmetry, thick eye brows, micrognathia, apparently lowset ears, an enormous abdominal wall defect, severe kyphoscoliosis, camptodactyly of the fingers, complete absence of the left lower limb, and absence of the lower part of the sacrum and coccyx, as well as left side of the pelvis. There was a disorganized appearance of the right foot with supernumerary digits and appendages and talipes equinovarus. No obvious amniotic bands or oligohydramnios were noted. Similar cases in the literature are reviewed and the clinical significance to genetic counselling is emphasized. © 1995 Wiley‐Liss, Inc.
Prenatal diagnosis of the urea cycle diseases: A survey of the european cases
Authors: Kamoun P. , Fensom A. H. , Shin Y. S. , Bakker E. , Colombo J. P. , Munnich A. , Bird S. , Canini S. , Huijmans J. G. M. , Chadefaux‐Vekemans B. , Whitfield A. E. , Kleijer W. J.
Published: June 2005

A European survey of prenatal diagnosis cases involving urea cycle diseases was performed. Citrullinemia was the most frequently investigated disease (108 cases). Other diseases are, in order of frequency, argininosuccinic aciduria (75 cases), ornithine transcarbamylase defect (52 cases), carbamoylphosphate synthetase defect (8 cases), triple H (3 cases), and arginase deficiency (1 case). Only one disease (ornithine transcarbamylase defect) is presently diagnosed using molecular biology methods. © 1995 Wiley‐Liss, Inc.
Absent tibiae—polydactyly—triphalangeal thumbs with fibular dimelia: Variable expression of the Werner (McKusick 188770) syndrome?
Authors: Vargas Fernando Regla , Pontes Ricardo Lopes , Llerena Juan Clinton , de Almeida Jose Carlos Cabral
Published: June 2005

We report on a family in which the autosomal dominant Werner syndrome (WS) (MIM# 188770) affects ten members in three generations. Besides the absent tibiae the propositus had duplication of the fibulae. Possible pathogenetic mechanism is discussed. © 1995 Wiley‐Liss, Inc.
Summary of the 1993 ASHG ancillary meeting “recent research on chromosome 4p syndromes and genes”
Authors: Estabrooks Laurel L. , Breg W. Roy , Hayden Michael R. , Ledbetter David H. , Myers Richard M. , Wyandt Herman E. , Yang‐Feng Teresa L. , Hirschhorn Kurt
Published: June 2005

The following is a summary of presentations given during an ancillary meeting to the 1993 American Society of Human Genetics Meeting in New Orleans, LA. This ancillary meeting, entitled “Recent Research on Chromosome 4p Syndromes and Genes,” reviewed the history of the Wolf‐Hirschhorn syndrome (WHS), the natural history of patients with WHS, and the smallest region of deletion associated with the WHS. The proximal 4p deletion syndrome and the duplication 4p syndrome were also described and advice was offered regarding detection of chromosome 4p deletions, duplications, and rearrangements. The current status of the physical map of chromosome 4p with emphasis on the genes that map to the 4p16 region was presented along with a preliminary phenotypic map of 4p16. The goal of this format was to provide a comprehensive review of the clinical presentations, diagnostic capabilities, and genetic mapping advances involving chromosome 4p. © 1995 Wiley‐Liss, Inc.
Syndromal frontonasal dysostosis in a child with a complex translocation involving chromosomes 3, 7, and 11
Authors: Stevens Cathy A. , Qumsiyeh Mazin B.
Published: June 2005

We report on a 4‐year‐old boy with typical frontonasal dysostosis and an apparently balanced de novo translocation involving chromosomes 3, 7, and 11, and four breakpoints. The karyotype was 46,XY,t(7;3)(3;11) (7pter→7q21.3::3q27→3qter;3pter→3q23::11q21→11qter;11pter→11q21::3q23→3q27::7q21.3→7qter). In situ hybridization with a chromosome 3 painting probe confirmed the interpretation from GTG banding. The child had a widow's peak, marked hypertelorism, absence of the nasal tip, and widely separated nares. He also had an atrial septal defect, micropenis, small testes, clubfeet, scoliosis, block C2–4, and structural brain abnormalities on MRI. In review we found two other cases of frontonasal dysostosis with chromosome abnormalities, neither of which was similar to our case. The presence of a denovo (apparently) balanced translocation in our patient may help to locate the gene(s) for frontonasal dysplasia and perhaps other midline craniofacial malformations. © 1995 Wiley‐Liss, Inc.
Anterior cervical hypertrichosis: A dominantly inherited isolated defect
Authors: Braddock Stephen R. , Jones Kenneth Lyons , Bird Lynne M. , Villegas Isidro , Jones Marilyn C.
Published: June 2005

We present a sporadic case of nonsyndromal anterior cervical hypertrichosis and review the literature. Based on prior documentation of dominant inheritance it is suggested that this case may be the result of a fresh mutation associated with older paternal age. © 1995 Wiley‐Liss, Inc.
Mild phenotypic effects of a de novo deletion Xpter→Xp22.3 and duplication 3pter→3p23
Authors: Kulharya Anita S. , Roop Heidi , Kukolich Mary K. , Nachtman Ronald G. , Belmont John W. , Garcia‐Heras Jaime
Published: June 2005

We report on a girl with a de novo mono‐somy Xpter→Xp22.3 and trisomy 3pter→3p23, normal development and stature, mildly affected phenotype, and learning disabilities with a low normal level of intelligence. Late replication studies using BudR demonstrated that the entire der(X) was inactive in 30% of cells. In 62% of cells the inactivation did not spread to the autosomal segment in the der(X). The normal X was inactivated in 8% of cells. Quantitative X‐inactivation studies using the human androgen receptor locus assay (HAR) on peripheral leukocytes and buccal epithelial cells showed extreme skewing of methylation (90.4% of the paternal allele). The correlation of cytogenetic and molecular data suggest that the mild phenotype of the proposita is most likely due to preferential inactivation of the entire der(X), which seems to be of paternal origin. © 1995 Wiley‐Liss, Inc.
Upper limb malformations in DiGeorge syndrome
Authors: Cormier‐Daire V. , Iserin L. , Théophile D. , Sidi D. , Vervel C. , Padovani J. P. , Vekemans M. , Munnich A. , Lyonnet S.
Published: June 2005

We report on upper limb anomalies in two children with a complete DiGeorge sequence: conotruncal defects, hypocalcemia, thymic aplasia, and facial anomalies. One child had preaxial polydactyly, and the other had club hands with hypoplastic first metacarpal. In both patients, molecular analysis documented a 22qll deletion. To our knowledge, limb anomalies have rarely been reported in DiGeorge syndrome, and they illustrate the variable clinical expression of chromosome 22qll deletions. © 1995 Wiley‐Liss, Inc.
Lymphangiosarcoma in late‐onset hereditary lymphedema: Case report and nosological implications
Authors: Andersson Hans C. , Parry Dilys M. , Mulvihill John J.
Published: June 2005

Hereditary lymphedemas that are not associated with other malformations usually affect the lower limbs and are inherited in an autosomal dominant fashion. These non‐syndromic hereditary lymphedemas are categorized by their age of onset, being either congenital (Milroy disease) or having an onset in childhood or around puberty (Meige disease). We describe a family in which three individuals in three generations had unusually late onset of lym‐phedema in their mid‐twenties or thirties. The proband additionally developed a very rare lymphangiosarcoma. This tumor, usually associated with post‐mastectomy lym‐phedema, has not been described in late‐onset hereditary lymphedema. Because of an unusually high incidence of multiple primary tumors in association with lymphangiosarcoma in the literature (approximately 10%) and the proband's own familial cancer background, we speculate that an inherited predisposition to malignancy may underlie the development of lymphedema‐associated lymphangiosarcoma. © 1995 Wiley‐Liss, Inc.
Premature centromere division: A possible manifestation of chromosome instability
Authors: Méhes K. , Bühler Erica M.
Published: June 2005

Retrospective analysis of “routine” chromosome preparations from 2 patients with Fanconi anemia and 2 others with ataxia‐teleangiectasia showed increased chromosome breakage and a tendency to premature centromere division (PCD) with special reference to early separation of the large aero‐centric (13–15) chromosomes. The findings suggest that PCD may be a manifestation of chromosome instability related to potential malignancy. © 1995 Wiley‐Liss, Inc.
Somatic mosaicism for a DMD gene deletion
Authors: Saito Kayoko , Ikeya Kiyoko , Kondo Eri , Komine Satoshi , Komine Maki , Osawa Makiko , Aikawa Eizou , Fukuyama Yukio
Published: June 2005

Mosaicism is a mixed state, with two cell populations of different genetic origins caused by a cell mutation occurring after fertilization. In the present case, DNA analysis of lymphocytes led to a DMD diagnosis before death. Postmortem immunocyto‐chemical and DNA analysis showed somatic mosaicism. At age 18 years, blood lymphocyte DNA analysis showed a DMD gene deletion, upstream from exon 7 to the 5′ end containing both muscle and brain promoters. As the patient's mother and elder sister had no deletions, he was considered to have a new mutation. Immunocytochemical studies of postmortem tissues showed that dystrophin was absent from the tongue, deltoid, intercostal, psoas and rectus femoris muscles, but there was a mix of dystrophin‐positive and negative fibers in the rectus abdominis, cardiac, temporalis and sternocleidomastoid muscles. All diaphragm cells were dystrophin positive. Polymerase chain reaction (PCR) amplification from all tissues except the temporalis and sternocleidomastoid muscles, diaphragm and kidney, in which no deletion was found, showed the deletion from at least exon 6 to the 5′ end containing both muscle and brain promoters. In this case, a genomic deletion of the DMD gene contributed to the formation of tissues derived from both ectoderm and endoderm, and cells of mesodermal origin showed geno‐typic and phenotypic heterogeneity. Our results indicate a mutation of the present case may have occurred just before the period of germ layer formation. © 1995 Wiley‐Liss, Inc.
X microchromosome with additional chromosome anomalies found in Ullrich‐Turner syndrome
Authors: Wydner Karen L. , Li Mengrong , Singer‐Granick Carol , Sciorra Leonard J. , Krueger Leslie J.
Published: June 2005

Using standard cytogenetic methods coupled with molecular techniques, the following karyotype mos 45,X/46,XXq+/46,X+mar (X)/47,XXq+,+mar(X), was identified in a patient with Ullrich‐Turner syndrome (UTS). High‐resolution banding (n = 650) of the metaphase chromosomes yielded a breakpoint at q28 on the Xq+ rearranged chromosome. FISH was used to determine the presence of Y‐containing DNA in the Xq+ and the mar(X) chromosomes. The following molecular probes were used: DYZ1, DYZ3, and spectrum orange WCP Y. The lack of specific hybridization of these probes was interpreted as a low risk of gonadoblastoma in this patient. Using X‐chromosome‐ and centromerespecific probes, FISH demonstrated the presence of hybridizing material on both rearranged chromosomes, the Xq+ and mar(X). Finally, we determined that the mar(X) and Xq+ chromosomes contained telomeres in the absence of any interstitial telomeric hybridizing material. A micro‐X chromosome is present in this UTS patient. Delineation of events leading toward the mechanisms responsible for the multiple DNA rearrangements required to generate the micro‐X and Xq+ chromosomes awaits future studies. © 1995 Wiley‐Liss, Inc.
New autosomal recessive form of amelia
Authors: Michaud Jacques , Filiatrault Denis , Dallaire Louis , Lambert Marie
Published: June 2005

Amelia is a rare, usually sporadic malformation. We report on a family in which three fetuses had amelia of the upper limbs and variable deficiency of the lower limbs. The fetuses also had minor facial anomalies. Recurrence of the condition in sibs of both sexes suggests autosomal recessive inheritance. Recurrent amelia has been documented in only a few families most often associated with a different set of malformations. Possibly, mutations in more than one gene with different modes of transmission can lead to this severe limb deficiency. We speculate that the mutation found in our cases interferes with formation of the apical ectodermal ridge in the upper limbs and results in its premature degeneration in the lower limbs. © 1995 Wiley‐Liss, Inc.
Renal tubular acidosis in the Silver‐Russell syndrome
Authors: Alvarenga Ramón , del Angel Ariadna González , del Castillo Victoria , de la Puente Silvestre García , Maulén Irene , Carnevale Alessandra
Published: June 2005

Several patients with the Silver‐Russell syndrome (SRS) attending our Genetics Clinic were diagnosed as having persistent metabolic acidosis. Since this abnormality has not been reported previously in the SRS, we reexamined 33 SRS patients to evaluate the frequency and type of metabolic acidosis, the clinical and laboratory findings, and the growth pattern in SRS patients with and without metabolic acidosis. Among them, 14 had a consistent decrease in HCO levels. Renal studies in acidotic patients showed urine pH of 5.8 and 24 h urine calcium of <2.4 mg/kg/24 h; serum creatinine, excretion of glucose, and aminoacids were normal, as were renal ultrasound and excretory urography findings. These data supported the diagnosis of renal tubular acidosis, probably type II; the patients were treated with oral bicarbonate and acidosis was corrected successfully. Clinical manifestations were similar in acidotic and non‐acidotic patients. The nutritional indices at diagnosis and at last evaluation (at least 8 months after diagnosis) were abnormally low in all patients; however, acidotic patients, treated with bicarbonate, showed an improvement of nutritional status particularly in the weight/height index, although the difference between groups after follow‐up did not reach statistical significance. We suggest that metabolic acidosis due to renal tubular acidosis, probably type II, may occur in children with the SRS and should be looked for and treated in all patients. © 1995 Wiley‐Liss, Inc.
Screening for mtDNA diabetes mutations in Pima Indians with NIDDM
Authors: Sepehrnia Bahman , Prezant Toni R. , Rotter Jerome I. , Pettitt David J. , Knowler William C. , Fischel‐Ghodsian Nathan
Published: June 2005

More than half of the Pima Indians over age 35 years have non‐insulin‐dependent (type II) diabetes mellitus (NIDDM). Extensive data indicate the importance of maternal diabetes in determining their risk for diabetes. Generally, the risk of having NIDDM is higher in patients with affected mothers than affected fathers. This has been attributed to intrauterine factors, but recently mitochondrial inheritance has been raised as an alternative hypothesis. In other populations, several families and individuals with diabetes due to a mitochondrial DNA point mutation at nucleotide 3243 in the tRNA leu(UUR) gene have been described, as has one family with a 10.4 kb mitochondrial DNA duplication/deletion. We tested whether these specific mitochondrial gene mutations could explain a portion of the excess maternal transmission seen in the Pima Indians. Mitochondrial DNA obtained from blood lymphocytes of 148 Pima Indians with NIDDM was screened both for the point mutation at nt 3243, and the 10.4 kb duplication/ deletion. Neither of these mutations was detected, and although a small proportion of the excess maternal transmission in Pima Indians could still be due to yet undescribed mitochondrial mutations or imprin‐ted nuclear genes, our data support the role of the intrauterine environment in this population. © 1995 Wiley‐Liss, Inc.
Non‐random X chromosome inactivation in an affected twin in a monozygotic twin pair discordant for Wiedemann‐Beckwith syndrome
Authors: Eliseörstavik Ragnhild , Tommerup Niels , Eiklid Kristin , Heleneörstavik Karen
Published: June 2005

Wiedemann‐Beckwith syndrome (WBS) is a syndrome including exomphalos, macroglossia, and generalized overgrowth. The locus has been assigned to 11p15.5, and genomic imprinting may play a part in the expression of one or more genes involved. Most cases are sporadic. An excess of female monozygotic twins discordant for WBS have been reported, and it has been proposed that this excess could be related to the process of X chromosome inactivation. We have therefore studied X chromosome inactivation in 13‐year‐old monozygotic twin girls who were discordant for WBS. In addition, both twins had Tourette syndrome. The twins were monochorionic and therefore the result of a late twinning process. This has also been the case in previously re‐ported discordant twin pairs with infor‐mation on placentation. X chromosome inactivation was determined in DNA from peripheral blood cells by PCR analysis at the androgen receptor locus. The affected twin had a completely skewed X inactiva‐tion, where the paternal allele was on the active X chromosome in all cells. The unaf‐fected twin had a moderately skewed X in‐activation in the same direction, whereas the mother had a random pattern. Further studies are necessary to establish a possible association between the expression of WBS and X chromosome inactivation. © 1995 Wiley‐Liss, Inc.
Identification of supernumerary ring chromosome 1 mosaicism using fluorescence in situ hybridization
Authors: Chen Harold , Tuck‐Muller Cathy M. , Batista Denise A. S. , Wertelecki Wladimir
Published: June 2005

We report on a 15‐year‐old black boy with severe mental retardation, multiple congenital anomalies, and a supernumerary ring chromosome mosaicism. Fluorescence in situ hybridization with a chromosome 1 painting probe (pBS1) identified the ring as derived from chromosome 1. The karyotype was 46,XY/47,XY,+r(1)(p13q23). A review showed 8 reports of ring chromosome 1. In 5 cases, the patients had a non‐supernumerary ring chromosome 1 resulting in partial monosomies of the short and/or long arm of chromosome 1. In 3 cases, the presence of a supernumerary ring resulted in partial trisomy of different segments of chromosome 1. In one of these cases the supernumerary ring was composed primarily of the centromere and the heterochromatic region of chromosome 1, resulting in normal phenotype. Our patient represents the third report of a supernumerary ring chromosome 1 resulting in abnormal phenotype. © 1995 Wiley‐Liss, Inc.
FISH analysis in Prader‐Willi and Angelman syndrome patients
Authors: Bettio D. , Rizzi N. , Giardino D. , Grugni G. , Briscioli V. , Selicorni A. , Carnevale F. , Larizza L.
Published: June 2005

We report on a combined high resolution cytogenetic and fluorescent in situ hybridization study (FISH) on 15 Prader‐Willi syndrome (PWS) and 14 Angelman syndrome (AS) patients. High resolution banding showed a microdeletion in the 15q11‐q13 region in 7 out of 15 PWS patients, and FISH analysis of the D15S11 and SNRPN cosmids demonstrated absence of the critical region in three additional cases. Likewise 8 out of 14 AS patients were found to be deleted with FISH, using the GABRB3 specific cosmid, whereas only 4 of them had a cytogenetically detectable deletion. © 1995 Wiley‐Liss, Inc.
Prenatal diagnosis of Smith‐Lemli‐Optiz syndrome
Authors: McGaughran J. M. , Clayton P. T. , Mills K. A. , Rimmer S. , Moore L. , Donnai D.
Published: June 2005

An abnormality in cholesterol synthesis was described recently in the Smith‐Lemli‐Opitz (SLO) syndrome. Here we describe how the application of this finding has enabled an accurate prenatal diagnosis. We also discuss the possible use of this test in detecting heterozygotes. © Wiley‐Liss, Inc.
Autosomal recessive Melnick‐Needles syndrome or ter Haar syndrome? Report of a patient and reappraisal of an earlier report
Authors: Hamel Ben C. J. , Draaisma Jos M. T. , Pinckers Alfred J. L. G. , Boetes Carla , Hoppe Rainer L. E. , Ropers Hans‐Hilger , Brunner Han G.
Published: June 2005

We report on a patient with congenital glaucoma, brachycephaly with flat occiput, large anterior fontanel, hypertelorism, anteverted nostrils, thoracolumbar kyphosis, prominent coccyx with skin fold, short hands and feet, flexion deformity of fingers, and clubfeet. He had a double‐outlet right ventricle with ventricular septal defect, and severe tricuspid insufficiency. Mild skeletal changes included short tubular bones, absence of distal phalanges of toes, caliber variation of ribs, and scalloping of the anterior surface of vertebrae. The patient died at age 21 months. He belongs to the same extended family as 3 similarly affected patients, previously described by ter Haar et al. [1982: Am J Med Genet 13:469–477] as representing an autosomal recessive form of Melnick‐Needles syndrome. We believe this diagnosis is no longer tenable. After having reviewed the relevant literature, we conclude that most probably we are dealing with a new autosomal recessive syndrome. We propose to name this entity ter Haar syndrome. © Wiley‐Liss, Inc.
Longitudinal observations on 15 children with Wiedemann‐Beckwith syndrome
Authors: Weng Elaine Y. , Moeschler John B. , Graham John M.
Published: June 2005

We conducted a follow‐up study on 15 patients with Wiedemann‐Beckwith syndrome (WBS) to further clarify major and minor diagnostic clinical characteristics and long‐term expectations for growth and development. We found patients with WBS tended to have polyhydramnios with large placentas which were almost twice normal placental weight. The large fetal size and polyhydramnios often resulted in early delivery with occasional perinatal mortality (three cases). Increased placental size, with associated polyhydramnios resulting in excessive umbilical cord length, may be useful in suspecting WBS prior to delivery, thereby facilitating perinatal management. The presence of abdominal wall defects and/or macroglossia may help to confirm the diagnosis. At birth, patients were almost 2 standard deviations above the expected mean for gestational age, length, and weight. This trend continued through early childhood and then excessive size became less dramatic with increasing age. We detected no cytogenetic variations in nine patients who had studies done and, to date, no tumors have been detected other than a gastric teratoma that was evident in one infant at birth. Longitudinally, the children have not had an unusual incidence of medical problems, and long‐term ultrasound monitoring was not burdensome to the families. In comparison, mental and social development to unaffected siblings and cousins appeared normal. © 1995 Wiley‐Liss, Inc.
Primary midline developmental field. II. Clinical/epidemiological analysis of alteration of laterality (normal body symmetry and asymmetry)
Authors: Martínez‐Frías María‐Luisa , Urioste Miguel , Bermejo Eva , Rodríguez‐Pinilla Elvira , Félix Valentín , Paisán Luis , Martínez Salvador , Egüés Javier , Gómez Francisco , Aparicio Paulino , Cucalón Fermín , Arroyo Antonio , Meipp Christian , Vázquez Socorro , Rodríguez José Ignacio , Rosa Alejandro , García José , Jiménez Nicolás , Moro Carmen
Published: June 2005

Lubinsky [Am J Med Genet 3: 23–28, 1987] has suggested that the properties of the midline involve early determinative informational processes and are related to the midline's position and definition of the body's plane of symmetry. Opitz [Am J Med Genet 21: 175‐176, 1985, BD: OAS XXIX(1): 3–37 1993] has pointed out that the laterality sequences represent a midline developmental field complex. Thus, bilateral left‐sidedness (with asplenia) and bilateral right‐sidedness (with polysplenia) have been considered laterality sequences or syndromes if cause is known.

Using the malformed infants registered by the Spanish Collaborative Study of Congenital Malformations (ECEMC), we performed a clinical/epidemiological analysis of the relationship between midline defects and alteration of normal body asymmetry and symmetry. The results support the assumption that both conditions could be consequence of disturbances in the midline primary developmental field. © 1995 Wiley‐Liss, Inc.
Tay‐sachs disease in persons of French‐Canadian heritage in northern New England
Authors: Palomaki Glenn E. , Williams Josephine , Haddow James E. , Natowicz Marvin R.
Published: June 2005

This study sought to determine whether persons of French‐Canadian heritage in northern New England are at high risk for the lethal infantile form of Tay‐Sachs disease. In order to accomplish this, death records and laboratory diagnostic records were surveyed to ascertain Tay‐Sachs deaths in a cohort of 372,000 live births between 1977–1986. The proportion of the total population with French‐Canadian or Jewish heritage was determined from census and birth records, and the ethnic background of Tay‐Sachs cases was determined from the corresponding birth records. In 1,860 births, both parents were of Ashkenazi Jewish heritage. One of those children was diagnosed with Tay‐Sachs disease. In 41,000 births, both parents were of French‐Canadian heritage, and in an additional 93,000 births, one parent was of French‐Canadian heritage. No cases of Tay‐Sachs disease were identified in the offspring of those individuals. Approximately 14 cases (95% confidence interval 8–20) would be expected, if the gene frequency approximated that reported for individuals of Ashkenazi Jewish heritage. Based on the results of this study, routine testing for Tay‐Sachs disease heterozygosity is not indicated for persons of French‐Canadian heritage in northern New England. This conclusion may not necessarily be valid for persons of French‐Canadian heritage residing in other states. Further studies of Tay‐Sachs disease mutations and prevalence among persons of French‐Canadian heritage will be important to determine possible regional variations in gene frequencies. © 1995 Wiley‐Liss, Inc.
Familial occurrence of patent ductus arteriosus
Authors: Sletten Lisa J. , Pierpont Mary Ella M.
Published: June 2005

We describe 7 relatives with patent ductus arteriosus (PDA) and a slightly unusual facial appearance with prominent midface with nose elongation and flattening of the nasal bridge, wide‐set eyes, downturned palpebral fissures, mild ptosis, thickened lips, and apparently slightly low‐set ears. Autosomal dominant inheritance is suggested in this family. Other families where affected members have PDA and a similar facial appearance and autosomal dominant inheritance were described previously by Char [1978: BD:OAS XIV (6B):303–305] and Temple [1992: Clin Dysmorphol 1:17‐21]. © 1995 Wiley‐Liss, Inc.
Use of fluorescence in situ hybridization to clarify a complex chromosomal rearrangement in a child with multiple congenital anomalies
Authors: Spikes Aimee S. , Hegmann Katherine , Smith Janice L. , Shaffer Lisa G.
Published: June 2005

A child with multiple congenital anomalies was referred for cytogenetic evaluation. G‐banded analysis showed a complex chromosome rearrangement involving 6 different chromosomes and 10 breakpoints. Fluorescence in situ hybridization (FISH) using whole chromosome painting probes and repetitive sequence probes was performed. In most cases the painting probes alone helped to clarify the G‐banded results. However, in one instance, where the terminal band of the long arm of chromosome I was involved, the use of a telomeric probe was essential in defining the rearrangement. © 1995 Wiley‐Liss, Inc.
Supernumerary inv dup(15) in a patient with Angelman syndrome and a deletion of 15q11–q13
Authors: Spinner Nancy B. , Zackai Elaine , Cheng Sou‐De , Knoll Joan H. M.
Published: June 2005

We have studied a patient with Angelman syndrome (AS) and a 47,XY,+inv dup(15) (pter→q11::q11→pter) karyotype. Molecular cytogenetic studies demonstrated that one of the apparently normal 15s was deleted at loci D15S9, GABRB3, and D15S12. There were no additional copies of these loci on the inv dup (15). The inv dup (15) contained only the pericentromeric sequence D15Z1. Quantitative DNA analysis confirmed these findings and documented a standard large deletion of sequences from 15q11‐q13, as usually seen in patients with AS. DNA methylation testing at D15S63 showed a deletion of the maternally derived chromosome. AS in this patient can be explained by the absence of DNA sequences from chromosome 15q11‐q13 on one of the apparently cytogenetically normal 15s, and not by the presence of an inv dup (15). This is the fourth patient with an inv dup (15) and AS or Prader Willi syndrome, who has been studied at the molecular level. In all cases an additional alteration of chromosome 15 was identified, which was hypothesized to be the cause of the disease. Patients with inv dup (15)s may be at increased risk for other chromosome abnormalities involving 15q11‐q13. © 1995 Wiley‐Liss, Inc.
Parental origin of the extra haploid chromosome set in triploidies diagnosed prenatally
Authors: Miny P. , Koppers B. , Dworniczak B. , Bogdanova N. , Holzgreve W. , Tercanli S. , Basaran S. , Rehder H. , Exeler R. , Horst J.
Published: June 2005

The parental origin of the additional chromosome complement in a total of 17 cases of triploidy was determined mainly using highly polymorphic microsatellites. Maternal origin of the triploidy was demonstrated in most cases. To the best of our knowledge, this is the first systematic evaluation of the parental origin of chromosome sets in fetuses who survived until a cytogenetic diagnosis was established. In contrast to previous investigations this study documented a predominance of maternal origin of the extra haploid set mainly due to longer survival time for digynic triploidies. The concept of 2 distinct fetal phenotypes in triploidy is clearly supported by this study. © 1995 Wiley‐Liss, Inc.
Neuronal ceroid‐lipofuscinosis: A clinical and morphological study of 19 patients
Authors: Nardocci Nardo , Verga M. Luisa , Binelli Simona , Zorzi Giovanna , Angelini Lucia , Bugiani Orso
Published: June 2005

We report on clinical, electrophysiological, neuroradiological, and morphological data from 19 patients with different types (late infantile, juvenile, and adult) of neuronal ceroid‐lipofuscinosis (NCL), observed in the last 10 years at the Neurological Institute of Milan.

Late Infantile NCL (LINCL) (8 patients, 4m/4f). Age at onset: 2–4 1/2 years. Seizures (6 patients) or decline of mental capacities (2 patients) were the presenting symptoms, followed by myoclonus and ataxia; visual loss and optic atrophy occurred in 6 patients within 3 years. All but 2 children became bedridden within 3 1/2 years. CT and MRI demonstrated different degrees of cerebral and cerebellar atrophy within 3 years from onset of the disease. Ultrastructural studies showed fingerprint profiles (FP) and osmiophilic bodies (OB) in circulating lymphocytes; curvilinear bodies (CB) and FP were detected in eccrine secretory cells.

Juvenile NCL (JNCL) (7 patients, 4m/3f). Age at onset: 6–9 years. Visual loss with retinal degeneration was the presenting symptoms, accompanied in all but 2 patients by slight mental impairment. Seizures occurred within 2–4 years. CT and MRI detected cerebral or cerebellar atrophy in those patients (5 patients) with a clinical follow‐up longer than 4 years. Electron microscopy showed FP on circulating lymphocytes, and both FP and CB on skin biopsy specimens.

Adult NCL (ANCL) (4 patients, 3 m/1f). Age at onset: 12–50 years. Progressive myoclonus epilepsy (1 patient) or dementia with motor disturbances (3 patients) were the clinical phenotypes of the disease. MRI demonstrated cerebral and cerebellar atrophy within 6 years from onset. Electron microscopy disclosed FP in cytoplasmic vacuoles inside eccrine secretory cells. © 1995 Wiley‐Liss, Inc.
Childhood neuronal ceroid‐lipofuscinoses in Argentina
Authors: Taratuto Ana Lia , Saccoliti María , Sevlever Gustavo , Ruggieri Victor , Arroyo Hugo , Herrero María , Massaro Mario , Fejerman Natalio
Published: June 2005

We report on 30 cases of neuronal ceroid lipofuscinoses (NCL), mainly diagnosed in 1985–1993 in Argentina, whose population is predominantly of European descent. Twenty‐four cases were late infantile Jansky‐Bielschowsky (LINCL) and 6 were juvenile Spielmeyer‐Vogt (JNCL). Sex ratio was female: male, 20:10. Age range and mean at onset and at diagnosis for the LINCL cases were 1–6 years, mean 3.1, and 2–11 years, mean 5.5, and for the JNCL cases, 5–9 years, mean 7, and 9–18 years, mean 13, respectively. Cases were referred for biopsy after neurological examination, and most included complete electrophysiological [electroencephalography (EEG) with photic stimulation, electroretinography (ERG), and visual‐evoked potential (VEP)], neuroimaging, and neurometabolic investigation. NCL was the first suspected clinical diagnosis, followed by mitochondrial encephalopathy in some cases of recent onset. Except for 1 case, clinical findings were homogeneous in LINCL, characterized by refractive epilepsy, mental regression and progressive deterioration, ataxia, myoclonia, and visual loss. Abnormal VEP, ERG, and EEG, with polyphasic high‐voltage spikes when photic stimulation was performed at low frequency, were observed. Visual impairment and retinitis pigmentosa were early manifestations in 4/6 JNCL, followed by mental abnormalities, motor deterioration, and myoclonic jerks, while 2/4 followed an atypical course. In both variants inheritance was autosomal‐recessive. Five out of 27 families had more than 1 affected member, 3 of whom were included in our series. Diagnosis was initially performed in conjunctival biopsy in 3 cases, skin in 5, muscle in 17, and brain in 5, though most cases had a concomitant biopsy from another tissue including nerve, and there was a single brain autopsy. In the LINCL variant, storage material was mainly curvilinear, also exhibiting dense areas and electron‐lucent vacuoles in 1 case. In addition to fingerprint profiles in 4/6 cases, JNCL biopsies presented curvilinear profiles in a skin biopsy in 1 case, and electronlucent vacuoles in 2 cases in a muscle and brain biopsy coexisting within the same inclusion, with the curvilinear profiles surrounded by a unit membrane, while the other 2/6 had granular osmiophilic inclusions with poorly defined rectilinear areas. The purpose of this report is to describe NCL in a country mainly populated by European descendants, in order to contribute data for further collaborative research. © 1995 Wiley‐Liss, Inc.
Classification of the neuronal ceroid‐lipofuscinoses: Expansion of the atypical forms
Authors: Dyken Paul , Wisniewski Krystyna
Published: June 2005

The neuronal ceroid‐lipofuscinoses (NCL) are a group of different genetic diseases. The major types of NCL are expressed by six forms which represent different clinicopathologic and genetic forms. These are CLN‐1, Infantile; CLN‐2, Late Infantile; CLN‐3, Juvenile; CLN‐4, Adult‐Recessive; CLN‐5, Adult‐Dominant; and CLN‐6, Early Juvenile. The distinction between CLN‐4 and CLN‐5 is still disputatious. CLN‐6 has been called CLN‐5.

A seventh classification of NCL represents from 12 to 20% of those afflicted. This group consists of an extensive array of atypical types of ceroid‐lipofuscin accumulation in the secondary lysosomes of neurons and cells of other tissues (e.g., skin, conjunctiva, and lymphocytes) or by presumed clinical and genetic relationships. The authors have identified 15 atypical subtypes of NCL. These as a group are here described as a seventh form. Further biochemical, molecular, and genetic studies will identify more precisely the phenotypic and genotypic expression of these “minor” forms of NCL. © 1995 Wiley‐Liss, Inc.
New spielmeyer‐vogt variant with granular inclusions and early brain atrophy
Authors: Philippart Michel , Chugani Harry T. , Bateman J. Bronwyn
Published: June 2005

Three females in 2 families were originally diagnosed with Spielmeyer‐Vogt disease (SVD). The clinical course was different from SVD, with vision well preserved until age 10 years, and learning rather than visual difficulties the marker at the onset. Later, regression was unusually rapid, including global dementia, blindness, aphasia, and finally loss of self‐feeding and ambulation between ages 12–18 years. MRI scan in patient 3 documented brain atrophy between ages 8–10 years. Position Emission Tomography (PET) scanning with fluorodeoxyglucose in patients 2 and 3 showed diffusely decreased or absent cortical glucose metabolism, comparable at ages 12 and 18 years, respectively, to the results found in the oldest typical SVD case tested at age 29 years. Fine granular inclusions, instead of the expected fingerprint inclusions, were demonstrated by electron microscopy of lymphocytes, conjunctiva, and skin. Usual markers on chromosome 16p12 were not present in the first family tested. The clinical course, with nonspecific initial behavior difficulties, late onset of visual decline followed by fast global regression, progressive brain atrophy, decreased cortical glucose utilization as shown by PET scanning, and granular tissue inclusions, suggest a genetic variant of SVD. © 1995 Wiley‐Liss, Inc.
Immunocytochemical studies in the ceroid‐lipofuscinoses (Batten disease) using antibodies to subunit c of mitochondrial ATP synthase
Authors: Westlake Valerie J. , Jolly Robert D. , Bayliss Sheryl L. , Palmer David N.
Published: June 2005

Immunocytochemistry, using antibodies against subunit c of mitochondrial ATP synthase, has been carried out in the ovine, canine, late infantile, and adult forms of ceroid‐lipofuscinosis. Intensity of staining varied depending on the particular disease, species, fixation regime, and the antibody used. Differential staining of storage cytosomes in neurons of affected sheep and those in the late infantile patient suggested exposure of different epitopes. This was supported by the variable staining using two different antibodies in ovine, late infantile, and adult onset (Kufs) diseases. Immunostaining of muscle in the late infantile, and muscle and ear cartilage in affected sheep can assist diagnosis but positive results may depend on the age of the patient, at least in the latter species. In these tissues there was immunostaining of structures not identified by histochemical or fluorescence microscopy in addition to storage cytosomes that could be identified by these means. Poor or no immunostaining occurred with canine tissues. At the ultrastructural level, storage cytosomes but not other organelles stained with the immunogold method. © 1995 Wiley‐Liss, Inc.
Circadian rhythm studies in neuronal ceroid‐lipofuscinosis (NCL)
Authors: Heikkilä Erika , Hàtònen Taina H. , Telakivi Tiina , Laakso Maija‐Liisa , Heiskala Hannu , Salmi Tapani , Alila Aino , Santavuori Pirkko
Published: June 2005

Sleep disorders are common in NCL patients. The patients have problems such as frequent awakenings, difficulties with sleep onset, nightmares, and night terrors. The aim of the study was to examine whether the sleep disturbance in NCL can be explained on the basis of desynchronised circadian rhythms. Therefore we studied diurnal patterns of melatonin, cortisol, body temperature, and motor activity of 14 patients.

The group consisted of 8 JNCL patients, 5 INCL children, and one boy with Jansky‐Bielschowsky disease of the variant type. There were healthy age‐ and sex‐matched control subjects. The blood samples for serum melatonin and cortisol were collected every 2 hours during 24‐hour periods. Body temperature was recorded continuously for a 24‐hour period by a polygraph. Diurnal motor activity was measured by wrist actigraphy for 5 days.

In most of our patients sleep was fragmented and the sleep phase was irregular.

Disturbances in the daily hormonal rhythms occurred only in the minority of the patients and only at an advanced stage of the disease. Although disturbances in the body temperature rhythm were found in about half of the patients, a general failure in the circadian regulatory system does not explain the frequent disturbances of the sleep‐wake cycle of the NCL patients. © 1995 Wiley‐Liss, Inc.
Rapid detection of subunit c of mitochondrial ATP synthase in urine as a diagnostic screening method for neuronal ceroid‐lipofuscinoses
Authors: Wisniewski Krystyna E. , Kaczmarski Wojciech , Golabek Adam A. , Kida Elzbieta
Published: June 2005

Using Western blot analysis and the ELISA technique, we showed previously significantly higher levels of subunit c in the urine of individuals with late‐infantile neuronal ceroid lipofuscinosis (LINCL) and some patients with juvenile NCL (JNCL) [Wisniewski et al., J Inherited Metab Dis 17:205–210, 1994]. In an attempt to develop a diagnostic screening test for NCL based on detection of this biochemical marker in urine, we analyzed, using the blotting technique, urine from 7 infantile NCL (INCL), 17 LINCL, and 19 JNCL cases, 30 obligate heterozygotes, and 60 control cases. This analysis confirmed our former data showing significantly higher levels of subunit c in the urine from all LINCL and some JNCL cases. No false positive results were found. This simple analytical method may serve as a fast, non‐invasive screening test for NCL. © 1995 Wiley‐Liss, Inc.