bluuebunny/crossref_metadata_2025 huggingface dataset:
Eleven polish patients with microcephaly, immunodeficiency, and chromosomal instability: The Nijmegen breakage syndrome
Authors: Chrzanowska K. H. , Kleijer W. J. , Krajewska‐Walasek M. , Białecka M. , Gutkowska A. , Goryluk‐Kozakiewicz B. , Michałkiewicz J. , Stachowski J. , Gregorek H. , Łysón‐Wojciechowska G. , Janowicz W. , Jóźwiak S.
Published: June 2005

We report on 11 patients from 8 independent families (3 pairs of sibs) with a complex clinical pattern including microcephaly, peculiar “bird‐like” face, growth retardation, and, in some cases, mild‐to‐moderate mental deficiency. Most of the patients have recurring respiratory tract infections. One girl has developed B‐cell lymphoma. A detailed anthropometric study of 15 physical parameters, including 3 cephalic traits, was performed. It was possible to study the chromosomes of PHA‐stimulated lymphocytes in all of the patients. We found structural aberrations with multiple rearrangements, preferentially involving chromosomes 7 and 14 in a proportion of metaphases in all individuals. Profound humoral and cellular immune defects were observed. Serum AFP levels were within normal range. Radioresis‐tant DNA synthesis was strongly increased in all 8 patients who were hitherto studied in this respect. Our patients fulfill the criteria of the Nijmegen breakage syndrome, which belongs to the growing category of ataxia telangiectasia‐related genetic disorders. In light of the increased predisposition to malignancy in this syndrome, an accurate diagnosis is important for the patient. © 1995 Wiley‐Liss, Inc.
Autosomal‐recessive inheritance of benign recurrent intrahepatic cholestasis
Authors: de Koning Tom J. , Sandkuijl Lodewijk A. , de Schryver Jan E. A. R. , Hennekam Eric A. M. , Beemer Frits A. , Houwen Roderick H. J.
Published: June 2005

Benign recurrent intrahepatic cholestasis BRIO is a rare disorder characterized by recurrent episodes of cholestasis without permanent liver damage. Familial and sporadic cases have been described. Based on existing evidence, both autosomal‐recessive and autosomal‐dominant inheritance have been considered. We describe a large Dutch pedigree with 4 patients, strongly suggesting autosomal‐recessive inheritance. © 1995 Wiley‐Liss, Inc.
Cytogenetic and molecular analysis of a ring (21) in a patient with partial trisomy 21 and megakaryocytic leukemia
Authors: Palmer C. G. , Blouin J.‐L. , Bull M. J. , Breitfeld P. , Vance G. H. , Van Meter T. , Weaver D. D. , Heerema N. A. , Colbern S. G. , Korenberg J. R. , Antonarakis S. E. , Chen X.
Published: June 2005

We describe a patient with an asymmetric double ring 21 in mosaic form, 45,XX,‐21/46, XX,‐21,+r(21), who has limited manifestations of Down syndrome and who developed acute myelofibrosis and megakaryocytic leukemia (AMKL), FAB M7, a hematologic disorder particularly common in Down syndrome patients. In situ hybridization studies, gene dosage, and DNA polymorphism analysis showed that the ring chromosome carries a duplicated region which extends from D21S406 on the centromeric side and includes marker D21S3 on the telomeric side. FISH studies indicate two sizes of ring 21 in the patient. The origin of the supernumerary chromosome 21 in the proband was paternal; furthermore, the r(21) probably was formed postzygotically. Included in the duplicated segment are the candidate genes for leukemia AML‐1, ETS, and ERG. The potential significance of disomic homozygosity of loci on 21q in M7 megakaryocytic leukemia is discussed. © 1995 Wiley‐Liss, Inc.
Association between alleles of the transforming growth factor alpha locus and cleft lip and palate in the chilean population
Authors: Jara Lilian , Blanco Rafael , Chiffelle Italo , Palomino Hernan , Carreño Hernan
Published: June 2005

Two RFLPs at the TGFA locus were studied in 39 unrelated Chilean (Caucasoid‐Mongoloid) patients with non‐syndromic cleft lip/palate [CL(P)] and 51 control individuals. A highly significant association between BamHI A2 allele and CL(P) was detected (χ2 = 6.00; P = 0.014), while no association was found between TaqI RFLPs and clefting.

No significant differences were found when comparing genotypes by type of cleft and a positive or negative family history of clefting. Our results seem to support rather definitively the association between TGFA and clefting but do not support the hypothesis that TGFA is a major causal gene of CL(P). © 1995 Wiley‐Liss, Inc.
Satoyoshi syndrome: An unusual postnatal multisystemic disorder
Authors: Ehlayel Mohammad S. , Lacassie Yves
Published: June 2005

Satoyoshi syndrome is a rare disorder of unknown cause characterized by progressive, painful intermittent muscle spasms, malabsorption, alopecia, amenorrhea, and skeletal abnormalities mimicking a skeletal dysplasia. We describe a 19‐year‐old Caucasian woman with characteristic manifestations starting at age 9. The report of this patient confirms that this condition is not limited to the Asian population. © 1995 Wiley‐Liss, Inc.
Velo‐facio‐skeletal syndrome in a mother and daughter
Authors: Teebi Ahmad S. , Qumsiyeh Mazin B. , Meyers‐Seifer Cynthia H. , Meyn M. Stephen
Published: June 2005

We present a woman and her daughter with an apparently new short stature syndrome associated with facial and skeletal anomalies and hypernasality. Manifestations included hypertelorism with broad and high nasal bridge, epicanthal folds, narrow and high arched palate, mild mesomelic brachymelia, short broad hands, prominent finger pads, hyperextensibility of hand joints, small feet, nasal voice, and normal intelligence. The mother had short stubby thumbs and the daughter had posteriorly angulated ears and delayed bone age. The morphology of the nose and the hypernasality are reminiscent to those in the velo‐cardio‐facial syndrome. High resolution banding and fluorescent in situ hybridization studies showed no evidence of 22q11 deletions. Differentiation from Aarskog syndrome and Robinow syndrome is discussed. © 1995 Wiley‐Liss, Inc.
Kaufman oculocerebrofacial syndrome in a girl of 15 years
Authors: Briscioli V. , Manoukian S. , Selicorni A. , Livini E. , Lalatta F.
Published: June 2005

Kaufman oculocerebrofacial syndrome (KOS) is a rare autosomal recessive disorder characterized by severe mental retardation, microcephaly, long narrow face, ocular anomalies, and long thin hands and feet. To our knowledge only 8 cases have been reported so far, diagnosed at a mean age of 10 years. We report on a girl who was diagnosed at 15 years. Further phenotypic delineation is needed to improve diagnosis of this syndrome early in life. © 1995 Wiley‐Liss, Inc.
Hereditary disorders among Iranian Jews
Authors: Zlotogora Joël
Published: June 2005

Iranian Jews represent an ancient community with a very high degree of inbreeding. Although the community remained relatively isolated, it had strong ties with Babylonian Jewry in Iraq. Several genetic disorders have been reported to be frequent among Iranian Jews, in particular, corticosterone methyloxydase deficiency type II, polyglandular syndrome, and rimmed vacuole myopathy. Based on the data collected in our clinic, recessive and dominant deafness also appear to be frequent. Other diseases, such as β‐thalassemia, achromatopsia, colobomatous microphthalmia, Dubin‐Johnson syndrome, and congenital myasthenia gravis, were frequent in both the Iranian and Iraqi Jewish communities.

The place of origin of the families within Iran and the results of molecular studies suggest some reason(s) for the high frequency of these disorders among Iranian Jews. While the high frequency of some of the disorders, such as corticosterone methyloxydase deficiency type II, represents a founder effect, in other diseases (such as β‐thalassemia) it was secondary to heterozygote advantage. © 1995 Wiley‐Liss, Inc.
Photoanthropometric study of craniofacial traits of individuals with Prader‐Willi syndrome
Authors: Butler Merlin G. , Levine Gabrielle J. , Le Jacqueline Y. , Hall Bryan D. , Cassidy Suzanne B.
Published: June 2005

A photoanthropometric method, which enables an objective description of facial structures, was used to better delineate the craniofacial characteristics of 37 individuals with Prader‐Willi syndrome (PWS; 21 males and 16 females; 22 with 15q11q13 deletions and 15 with normal‐appearing chromosome 15s) between the ages of 0 to 12 years. Facial parameters were measured from strict frontal and profile photographic 35 mm slides and compared with other facial measurements from the same face (e.g., palpebral fissure width to bizygomatic diameter). We studied 16 photoanthropometric craniofacial indices following the protocols established by Stengel‐Rutkowski et al. [1984: Hum Genet 67:272–295] and Butler et al. [1988: Am J Med Genet 30:165–168]. Based on our measurements of 37 Prader‐Willi syndrome individuals, none of the parameters were consistently outside of the normal range when compared with photoanthropometric index standards for age established from white control children [Stengel‐Rutkowski et al., 1984]. However, several suggestive findings were documented by our analysis including: narrow palpebral fissure width [particularly in older children (6–12 years)], high midface, broad interalar distance, short back of the nose, prominent high chin, and broad low‐set ears. No significant differences were found in craniofacial parameters between deletion or nondeletion Prader‐Willi syndrome patients with this methodology. These craniofacial parameters (many not previously evaluated in PWS patients) may become useful for early detection, and aid in the diagnosis and the study of the development of the characteristic face seen in Prader‐Willi patients. © 1995 Wiley‐Liss, Inc.
Partial trisomy 13q identified by sequential fluorescence in situ hybridization
Authors: Rao V. V. N. Gopal , Carpenter Nancy J. , Gucsavas Muge , Coldwell James , Say Burhan
Published: June 2005

We report on a 19‐month‐old boy with partial trisomy 13q resulting from a probable balanced translocation involving chromosomes 1 and 13. The infant presented with omphalocele, malrotation, microcephaly with overriding skull bones, micrognathia, apparently low‐set ears, rocker‐bottom feet, and congenital heart disease, findings suggestive of trisomy 13. Karyotypic studies from peripheral blood lymphocytes documented an unbalanced karyotype 46,XY,−1, +der(1). The mother's chromosomes were normal, and the father was not available. Conventional cytogenetic techniques were unable to identify the extra material on the terminal 1q. Using fluorescence in situ hybridization (FISH) on the GTL‐banded metaphases, the extra material on 1q was identified as the terminal long arm of 13, thus resulting in partial trisomy 13 (q32–qter). © 1995 Wiley‐Liss, Inc.
Identical twins with Cohen syndrome
Authors: North Kathryn N. , Fulton Anne B. , Whiteman David A. H.
Published: June 2005

We report the first case of identical female twins who satisfy the proposed diagnostic criteria for Cohen syndrome. The sisters presented with retinal degeneration, obesity and mental retardation, and had the characteristic facial appearance. The manifestations of previously reported cases of Cohen syndrome are reviewed. Unusual changes in our patients include tall stature, macrocephaly, and transient cardiomyopathy during the first year of life. These anomalies have been reported previously in other patients with Cohen syndrome, and suggest that the disorder is phenotypically heterogeneous. Precocious puberty was present in both girls; the latter findings have not been reported previously in the Cohen syndrome. Detailed metabolic and cytogenetic analysis demonstrated no abnormalities. © 1995 Wiley‐Liss, Inc.
Renal dysplasia associated with in utero exposure to gentamicin and corticosteroids
Authors: Hulton Sally‐Anne , Kaplan Bernard S.
Published: June 2005

We report on a patient with renal cystic dysplasia, whose mother was given gentamicin and corticosteroids early in pregnancy. We speculate that these drugs may be implicated in abnormal nephrogenesis in humans. This speculation is based on gentamicin‐induced small kidneys (oligonephronia) in the rat. Renal cystic disease has been demonstrated following glucocorticoid administration early in gestation. We realize that there is no proof for a causal relationship between gentamicin and/or glucocorticoids in the pathogenesis of this patient's renal disease. However, it is possible that renal cystic dysplasia in humans is not solely the result of a genetic defect. © 1995 Wiley‐Liss, Inc.
Apparently new “anophthalmia‐plus” syndrome in sibs
Authors: Fryns Jean‐Pierre , Legius Eric , Moerman Philippe , Vandenberghe Kamiel , Van den Berghe Herman
Published: June 2005

The index patient of this report is a 17‐weekgestation female fetus with bilateral anophthalmia, bilateral cleft lip/cleft palate, macrotia with bilateral lateral facial cleft, large open sacral neural tube defect, and uterus unicornis. Parents were normal and nonconsanguineous with an unremarkable family history. Their first child, a 4‐year‐old boy, is normal. The second child, a 2 ½‐year‐old boy, has bilateral anophthalmia and an abnormal left ear with absent lobule as the sole additional anomaly. These 2 sibs seem to be the first examples of a new “anophthalmia‐plus” syndrome apparently inherited as autosomal‐recessive. © 1995 Wiley‐Liss, Inc.
Distal arthrogryposis type IIB: Further clinical delineation and 54‐year follow‐up of an index case
Authors: Friedman B. D. , Heidenreich R. A.
Published: June 2005

Distal arthrogryposis IIB is characterized by contractures of the distal joints (especially of the fingers and toes) and ptosis. We recently encountered a father and son with these manifestations. The father was reported 54 years ago as a case of amyoplasia congenita (arthrogryposis multiplex congenita). Both father and son have distal joint contractures, most severe in the hands and feet, as well as ptosis and ophthalmoplegia. In addition, these patients have an unusual distribution of hair loss, and conical teeth. Whether these latter findings are related to the type of distal arthrogryposis present in this family is not known. In spite of their physical limitations both father and son have maintained an active life‐style. © 1995 Wiley‐Liss, Inc.
Linkage of preaxial polydactyly type 2 to 7q36
Authors: Hing Anne V. , Helms Cynthia , Slaugh Rachel , Burgess Andrea , Wang Jen C. , Herman Thomas , Dowton S. Bruce , Donis‐Keller Helen
Published: June 2005

We have characterized a 6‐generation North American Caucasian kindred segregating one form of preaxial polydactyly type 2 (PPD‐2). We demonstrate linkage to the 7q36 region and describe a submicroscopic telomeric chromosomal deletion in phase with the PPD‐2 phenotype. Recently, several kindreds segregating triphalangeal thumb (TPT) with and without associated hand anomalies (syndactyly and/or postaxial polydactyly) have also been linked to the subtelomeric region of chromosome 7q [Heutink et al., 1994: Nat Genet 6:287–291; Tsukurov et al., 1994: Nat Genet 6:282–286]. We demonstrate by haplotype analysis that our North American pedigree represents a PPD allele that is independent of the founder PPD allele present in the previously described kindreds. © 1995 Wiley‐Liss, Inc.
Microdontia with severe microcephaly and short stature in two brothers: Osteodysplastic primordial dwarfism with dental findings
Authors: Lin Henry J. , Sue Gregory Y. , Berkowitz Carol D. , Brasel Jo Anne , Lachman Ralph S.
Published: June 2005

Two brothers from a black family had microcephaly, short stature, and generalized microdontia. Endocrine and chromosome studies were normal, and mild skeletal manifestations were present. The patients may represent a distinct dental‐skeletal dysplasia, possibly osteodysplastic primordial dwarfism type II. Attention to dental manifestations in similar cases may be useful for classification. © 1995 Wiley‐Liss, Inc.
Clinical spectrum in homozygotes and compound heterozygotes inheriting cystic fibrosis mutation 3849+10kbC>T: Singnificance for geneticists
Authors: Gilbert Fred , Li Zhen , Arzimanoglou Iordanis , Bialer Martin , Denning Carolyn , Gorvoy Jack , Honorof Joyce , Ores Celia , Quittell Lynne , Rossoff Leonard , Valverde Kathleen
Published: June 2005

We describe patients inheriting cystic fibrosis (CF) mutation 3849+10kb>T as homozygotes of compound heterozygotes. Three unrelated homozygotes for this mutation were all pancreatic‐sufficient and sweat testnegative or inconclusive. Among the compound heterozygotes, both pancreatic sufficiency and insufficiency, as well as positive and negative/inconclusive sweat test results are reported, expanding the range of clinical expression associated with inheritance of this mutation. 3849+10kbC>T is one of several CF mutations that can result in atypical or variant forms of CF. For geneticists, the diagnosis of variant CF has implications for recurrence risk and prognosis counseling of the families of affected individuals, and possibly for CF carrier screening in the general population. © 1995 Wiley‐Liss, Inc.
Phenotypic manifestations of branchiootorenal syndrome
Authors: Chen Achih , Francis Mary , Ni Li , Cremers Cor W. R. J. , Kimberling William J. , Sato Yutaka , Phelps Peter D. , Bellman Susan C. , Wagner Michael J. , Pembrey Marcus , Smith Richard J. H.
Published: June 2005

Branchiootorenal (BOR) syndrome is a variable, autosomal‐dominant disorder of the first and second embryonic branchial arches, kidneys, and urinary tract. We describe the phenotype in 45 individuals, highlighting differences and similarities reported in other studies. Characteristic temporal bone findings include cochlear hypoplasia (4/5 of normal size with only 2 turns), dilation of the vestibular aqueduct, bulbous internal auditory canals, deep posterior fossae, and acutely‐angled promontories. © 1995 Wiley‐Liss, Inc.
Risk prediction with linked markers: Theory
Authors: Rogatko André
Published: June 2005

A Bayesian method to predict disease recurrence risks based on distance information between loci and allowing for uncertain gene location is presented. The methodology allows derivation of the posterior distribution of recurrence risks, from which point estimates and associated precision measures can be calculated. The resulting risk distribution accounts for all available information concerning location and relative distance, and can be updated as additional data become available. © 1995 Wiley‐Liss, Inc.
Asian hereditary neuropathy patients with peripheral myelin protein‐22 gene aneuploidy
Authors: Ohnishi Akio , Li Lan‐Ying , Fukushima Yoshimitsu , Mori Toshio , Mori Masataka , Endo Chiyoko , Yoshimura Takeo , Sonobe Masanobu , Flandermeyer Robert , Lebo Roger V.
Published: June 2005

Japanese hereditary neuropathy with liability to pressure palsy (HNPP) patients have a deletion of one peripheral myelin protein‐22 (PMP22) gene region in distal chromosome band 17p11.2 as do Caucasian patients. Japanese and Asiatic Indian CMT1A patients have a PMP22 gene duplication that results in Charcot‐Marie‐Tooth disease type IA (CMT1A; HMSNIA) in patients of European and Middle Eastern ancestry. About 70% of Japanese CMT1 patients have a PMP22 duplication as do Caucasians, while Japanese CMT1B, CMT2 and Dejerine‐Sottas patients do not have PMP22 gene region aneuploidy. Although HNPP and CMT1A genotypes are generated simultaneously by unequal recombination that results in PMP22 gene aneuploidy in each daughter cell, only 3 Japanese HNPP probands with PMP22 deletion from a large patient population were referred to a single center compared to 18 referred CMT1A probands with PMP22 duplication. This lower HNPP frequency more likely reflects lower HNPP reproductive fitness than patient ascertainment bias because disease severity and variation in severity is about the same in CMT1A and HNPP patients and because all patients of both types were referred regardless of disease severity. These results, along with an apparently high de novo CMT1A mutation rate, suggest that common ancestors of Japanese, Asian Indians, and Caucasians carried PMP22 geneflanking sequences that enhance unequal crossing over. © 1995 Wiley‐Liss, Inc.
Non‐cardiac malformations in individuals with outflow tract defects of the heart: The Baltimore‐Washington infant study (1981–1989)
Authors: Lurie I. W. , Kappetein A. P. , Loffredo C. A. , Ferencz C.
Published: June 2005

In the Baltimore‐Washington Infant Study, a regional case‐control study of 4,390 liveborn infants with cardiovascular malformations (CVM), 642 patients (14.2%) had outflow tract abnormalities, with extracardiac defects in 157 (∼25%) of them. Associated defects were found in 1/3 of patients with normal great arteries, but only in 1/10 of patients with transposition of great arteries (TGA). The extracardiac defects were especially rare in the groups “TGA with intact ventricular septum” and “TGA with ventricular septal defect.” Patients with multiple associated defects outnumbered patients with isolated associated defects in the ratio 2.5:1. The associated defects were heterogeneous: 46 patients had chromosome abnormalities, 16 had different Mendelian syndromes, and 36 had associations (DiGeorge sequence and VACTERL association were the most frequent). A new syndrome of multiple congenital abnormalities including tetralogy of Fallot, and rare cases of chromosomal and Mendelian syndromes (distal trisomy 1q, tetrasomy 8p, Holzgreve syndrome) are described briefly. Sufficient variability of a spectrum of conotruncal defects in the patients with the same chromosomal or Mendelian syndromes suggests that at least in some cases different conotruncal defects are stages of the same morphologic spectrum. The analysis of conotruncal defects in sibs of patients with Mendelian syndromes may provide new data about the links between different definitive forms of CVM. © 1995 Wiley‐Liss, Inc.
Aplasia cutis congenita associated with limb, eye, and brain anomalies in sibs: A variant of the Adams‐Oliver syndrome?
Authors: Örstavik Karen Helene , Strömme Petter , Spetalen Sigmund , Flage Tor , Westvik Jostein , Vesterhus Per , Skjeldal Ola
Published: June 2005

Aplasia cutis congenita (ACC) may occur in isolation or with other congenital malformations. Peripheral limb anomalies and ACC are major elements of the Adams‐Oliver syndrome, which is usually inherited as an autosomal dominant disorder. We report on a sister and brother with ACC and brain, eye, and transverse limb anomalies. The phalanges of the hands and feet were either short or absent. The girl also had absence of right patella, was severely mentally retarded and blind with retinal nonattachment. The boy had a falciform fold in the left eye. He died at age one week and autopsy showed partial agenesis of corpus callosum. The findings in the sibs may represent a severe variant of the Adams‐Oliver syndrome, or a previously unrecognized syndrome involving vascular disruption. © 1995 Wiley‐Liss, Inc.
Schinzel‐Giedion syndrome: Report of two sibs
Authors: Antich J. , Manzanares R. , Camarasa F. , Krauel X. , Vila J. , Cusi V.
Published: June 2005

We report on two further cases, a sister and a brother, with Schinzel‐Giedion syndrome. Both presented the following manifestations: “coarse face” with midface retraction, agenesis of corpus callosum, bilateral hydronephrosis, and typical skeletal anomalies. Patient 1 had a malignant sacrococcygeal teratoma. This is the third case of malignancy in this syndrome. Patient 2 died shortly after birth. © 1995 Wiley‐Liss, Inc.
Opitz GBBB syndrome: Chromosomal evidence of an X‐linked form
Authors: Verloes Alain , David Albert , Odent Sylvie , Toutain Annick , André Marie‐Joseph , Lucas Josette , Marec Bernard Le
Published: June 2005

BBB syndrome and G syndrome were originally reported as distinct X‐linked disorders. Clinical studies indicated that BBB and G syndromes were likely to represent variant expression of the same disorder, now referred to as “Optiz” GBBB syndrome. Several occurrences of male‐to‐male transmission in both syndromes led to the hypothesis that GBBB syndrome was a single autosomal dominant, sec influenced disorder, now tentatively mapped to 5p12‐13.

We report on a large pedigree in which GBBB syndrome appears to cosegregate with a pericentric inversion of the X chromosome inv(X)(p22.3q26). It indicates the possible existence of a true X‐linked form of GBBB syndrome, which does not appear phenotypically different from its autosomal counterpart. The gene could map in the vicinity of the breakpoints, in Xp or Xq. The existence of two genes affecting a common pathogenetic pathway could explain the gender‐dependent expressivity of GBBB phenotype. © 1995 Wiley‐Liss, Inc.
Spondyloperipheral dysplasia
Authors: Sorge G. , Ruggieri M. , Lachman R. S.
Published: June 2005

We present a patient with spondyloperipheral dysplasia, a rare skeletal dysplasia which is characterized by vertebral body abnormalities (platyspondyly, end‐plate indentations) and brachydactyly. Our patient also manifested a characteristic “pugilistic” face, sensorineural deafness and mental retardation. This chondroosseous dysplasia appears to be inherited as an autosomal dominant disorder. It appears that there is considerable clinical variability in spondyloperipheral dysplasia. © 1995 Wiley‐Liss, Inc.
Phenotypic differences among patients with Bardet‐Biedl syndrome linked to three different chromosome loci
Authors: Carmi Rivka , Elbedour Khalil , Stone Edwin M. , Sheffield Val C.
Published: June 2005

Bardet‐Biedl syndrome (BBS) is an autosomal‐recessive disorder of mental retardation, obesity, retinal dystrophy, polydactyly, and hypogenitalism. Renal and cardiac abnormalities are also frequent in this disorder. Previous clinical suggestions of heterogeneity of BBS were confirmed recently by the identification of four different chromosome loci linked to the disease. In this study we compared clinical manifestations of the syndrome in patients from 3 unrelated, extended Arab‐Bedouin kindreds which were used for the linkage mapping of the BBS loci to chromosomes 3, 15, and 16. The observed differences included the limb distribution of the postaxial polydactyly and the extent and age‐association of obesity. It appears that the chromosome 3 locus is associated with polydactyly of all four limbs, while polydactyly of the chromosome 15 type is mostly confined to the hands. On the other hand, the chromosome 15 type is associated with early‐onset morbid obesity, while the chromosome 16 type appears to present the “leanest” form of BBS. Future cloning of the various BB genes will contribute to the understanding of the molecular basis of limb development and to the identification of human obesity‐related genes. © 1995 Wiley‐Liss, Inc.
Autosomal dominant optic nerve colobomas, vesicoureteral reflux, and renal anomalies
Authors: Schimmenti Lisa A. , Pierpont Mary Ella , Carpenter Becky L. M. , Kashtan Clifford E. , Johnson Max R. , Dobyns William B.
Published: June 2005

We describe a father and 3 sons with optic nerve colobomas, vesicoureteral reflux, and renal anomalies. The youngest son had congenital renal failure and ultimately underwent renal transplantation. The father and one son had high frequency hearing loss. There were no other affected relatives. We conclude that the association of optic nerve colobomas, renal anomalies, and vesicoureteral reflux comprises a unique autosomal dominant syndrome. Molecular investigations have determined this disorder to be associated with a single nucleotide deletion in the PAX2 gene. © 1995 Wiley‐Liss, Inc.
Distinct craniofacial syndrome of lagophthalmia and bilateral cleft lip and palate
Authors: Korula Shirley , Wilson Libby , Salomonson Janet
Published: June 2005

We report on several individuals with bilateral cleft lip and palate, lagophthalmia, megaloblepharon, distichiasis, and ectropion of the lower eyelids, representing in total a distinct craniofacial syndrome. Eight cases (3 from 1 family) in ages ranging from 1–45 years were identified over a 7‐year period in the Cleft Palate and Craniofacial Clinic at our center. All cases (3 male, 5 female) presented with bilateral cleft lip and palate and lagophthalmia. Birth weight, growth, and development were normal in all cases, except for one who probably has familial small stature. Five of the 8 cases have distichiasis, and 5 have ectropion in varying degrees; dental findings consisted of hypodontia in 5 and delayed dentition in 1 patient. Hypoplastic nails and clinodactyly were confined to 3 members of 1 family. Clinical evidence in these cases and a review of the literature regarding distichiasis and lagophthalmia, either alone or in combination with ectropion, suggest that this craniofacial syndrome is most likely an autosomal‐dominant trait. The 5 non‐familial cases probably represent new mutations. © 1995 Wiley‐Liss, Inc.
Spondyloepimetaphyseal dysplasia with joint laxity (SEMDJL): Clinical and radiological findings in a guatemalan patient
Authors: Bradburn Joyce M. , Hall Bryan D.
Published: June 2005

We report on a patient of Guatemalan descent whose physical and radiological findings are consistent with a diagnosis of spondyloepimetaphyseal dysplasia with joint laxity (SEMDJL). This is a rare, autosomal recessive skeletal dysplasia with short limbs, severe scoliosis, high dorsal kyphoscoliosis, and joint hypermobility. Most described patients with SEMDJL are from the Afrikaans‐speaking communities of South Africa. Patients with SEMDJL have an oval face, prominent eyes, and blue sclerae. Our patient's height and weight were below the fifth centile. She had prominent eyes with blue sclerae, a narrow, high‐arched palate, pectus carinatum, severe scoliosis, and hyperextensibility and instability of most joint, with limited extension and supination of her elbows. A review of her roentgenograms showed severe scoliosis, poorly developed ischial, iliac, and pubic bones, a “bat‐like” appearance of the iliac bones, “dysplastic” acetabulum, minimal metaphyseal and epiphyseal abnormalities at the knees, deformation of the proximal femoral metaphyses, and generalized brachydactyly of the hands and feet. This disorder may be more common than previously thought, and the diagnosis should be considered in any child with a dwarfing considered in any child with a dwarfing condition and joint laxity. © 1995 Wiley‐Liss, Inc.
Evidence for a discrete behavioral phenotype in the oculocerebrorenal syndrome of lowe
Authors: Kenworthy Lauren , Charnas Lawrence
Published: June 2005

The oculocerebrorenal syndrome of Lowe (OCRL) is an X‐linked disorder characterized by congenital cataracts, cognitive impairment, and renal tubular dysfunction. Although there is a wide range of intellectual function in affected individuals, it is often compromised by a high prevalence of maladaptive behaviors, including tantrums, stubbornness, and stereotypy. Whether these behaviors simply reflect the multiple disabilities found in some developmentally impaired individuals with or without OCRL, or a specific genetically‐determined behavioral phenotype of OCRL, is unknown. Controls were matched for sex, age, visual impairment, and adaptive functioning and compared with OCRL patients on three standardized measures of adaptive/maladaptive behaviors. Forty‐three matched pairs of OCRL and control subjects were identified. Both groups were similar in communication, daily living, socialization, and motor skills, in socioeconomic status, and in measures of parental stress. Individuals with OCRL displayed significantly more severe maladaptive behaviors than control boys, as measured by the Vineland Adaptive Behavior Scales (VABS), with 41% of the difference between the two groups attributable to the diagnosis of OCRL. Twelve maladaptive behaviors measured on the VABS appeared more frequently in OCRL than in controls. Five of these 12 behaviors, i.e., temper tantrums, irritability, complex repetitive behaviors (stereotypy)/mannerisms, obsessions/unusual preoccupations, and negativism, were identified by discriminant function analysis to significantly distinguish between controls and OCRL individuals. The diagnosis of OCRL is associated with a behavioral phenotype consisting of temper tantrums, stereotypy, stubbornness, and obsessions/unusual preoccupations. This phenotype cannot be attributed solely to the visual, motor, and intellectual disabilities characteristic of OCRL, and may represent a specific effect of the OCRL gene on the central nervous system. © 1995 Wiley‐Liss, Inc.

This article is a U.S. Government work and, as such, is in the public domain in the United States of America.
FH Tulsa‐1 and ‐2: Two unique alleles for familial hypercholesterolemia presenting in an affected two‐year‐old African‐American male
Authors: Blackett Piers R. , Altmiller Dale H. , Jelley David , Wilson Don P.
Published: June 2005

A two‐year‐old African American boy presented with cutaneous xanthomata and extreme hypercholesterolemia. Subsequent studies revealed that the LDL‐cholesterol was 1,001 mg/dl and apoB 507 mg/dl. LDL‐receptor activity was almost undetectable, which is compatible with the finding of two newly described defective alleles on exon 4 of the LDL‐receptor gene coding for part of the ligand‐binding domain. One allele contained a 21 base‐pair insertion from codon 200 to 207 whereas the other had a point mutation at codon 207. The rarity of genes for FH reported in individuals of African ancestry is discussed. © 1995 Wiley‐Liss, Inc.
Prenatal diagnosis of familial dysautonomia by analysis of linked CA‐repeat polymorphisms on chromosome 9q31–q33
Authors: Eng Christine M. , Slaugenhaupt Susan A. , Blumenfeld Anat , Axelrod Felicia B. , Gusella James F. , Desnick Robert J.
Published: June 2005

Familial Dysautonomia (FD) is an autosomal recessive sensory neuropathy that affects about 1 in 3,700 individuals of Ashkenazi Jewish ancestry. The underlying biochemical and genetic defects are unknown, thereby precluding prenatal diagnosis in at‐risk families. Recently, the FD gene (DYS) was mapped with strong linkage disequilibrium to polymorphic markers in the chromosome 9 region q31–q33. In this report, the use of these markers for the prenatal diagnosis of FD by linkage analysis in families with a previously affected child was evaluated. Genomic DNA from appropriate family members was analyzed to construct haplotypes using informative CA repeat polymorphisms closely linked to and flanking the FD locus. The calculation of risk for the prenatal diagnoses was performed by linkage analysis. All seven FD families were informative for the closely linked polymorphic markers and fetal diagnoses were made in eight pregnancies. Six fetal diagnoses were predicted with >98% accuracy, while two with recombinations were predicted with at least 88% and 92% accuracy. Use of these closely linked markers permitted the reliable prenatal diagnosis of FD in families with a previously affected child. © 1995 Wiley‐Liss, Inc.
Factors which influence the rate of receiving a routine second newborn screening test in Washington State
Authors: Doyle Debra L. , Sanderson Maureen , Bentvelzen Johanneke , Fineman Robert M.
Published: June 2005

This study was conducted to determine whether newborns from different ethnic and socioeconomic groups in Washington State are equally likely to have a routine second newborn screening (NBS) test and if there are identifiable factors associated with not having a second test. For many years, the standard of care for NBS in Washington has been that newborns should receive a routine second screening test at age 7–10 days. However, data collected by State Department of Health (DOH) staff for the past several years indicate that only about 80% of newborns receive a routine second NBS test. The data presented here suggest that identifiable factors (i.e., barriers) exist in accessing a routine second NBS test in Washington. Increased educational efforts targeting certain high‐risk infants, their parents/caretakers, and primary care providers are apparently needed to ensure equal access to a routine second test. © 1995 Wiley‐Liss, Inc.
Dissemination of genetic risk information to relatives in the fragile X syndrome: Guidelines for genetic counselors
Authors: McConkie‐Rosell A. , Robinson H. , Wake S. , Staley L. W. , Heller K. , Cronister A.
Published: June 2005

Fragile X syndrome, which affects 1 in 1,250 males, is the most common inherited condition causing mental retardation. Although carrier detection for the fragile X syndrome utilizing DNA has now been simplified, genetic counseling and the process of informing at‐risk family members remains complex. The purpose of this paper is to offer practical guidelins to health professionals providing genetic counseling to fragile X families in order to facilitate the dissemination of genetic risk information to relatives. This paper was developed from a workshop held at the 4th International Fragile X Conference. The guidelines presented here represent a beginning in the development of an approach to informing relatives in fragile X familes about genetic risk, and the identification of mechanisms to reduce the burden to families. © 1995 Wiley‐Liss, Inc.
Infant with mos45,X/46,XY/47,XYY/48,XYYY: Genetic and clinical findings
Authors: Fox Joyce E. , Blumenthal Donna , Brock William , Kreitzer Paula , Cooper Rubin , Anderson Dennis , Pleak Richard , Ehrenfreund Linda , Freedman Samuel , Zaslav Ann‐Leslie
Published: June 2005

We describe an infant with mos45,X/46,XY/47,XYY/48,XYYY who presented with ambiguous genitalia. Her phenotype was also remarkable for minor ear and eye anomalies and coarctation of the aorta with bicuspid aortic valve. Laparoscopy revealed bilateral Fallopian tubes and a left infantile testis with epididymis. Chromosomal analyses of blood, skin, aorta, right Fallopian tube, and left gonadal tissue showed mos45,X/46,XY/47,XYY/48,XYYY. The 46,XY cell line was identified with routine trypsin‐Giemsa banding only in cultured cells from an aortic biopsy. Fluorescence in‐situ hybridization (FISH) was utilized to identify the presence of 46,XY cells in other tissues. The clinical manifestations of this patient are discussed and compared with those of similar cases of Y chromosome aneuploidy. To our knowledge, this is the first report of a patient with this unusual karyotype. © 1995 Wiley‐Liss, Inc.
Benzoate therapy and carnitine deficiency in non‐ketotic hyperglycinemia
Authors: Van Hove Johan L. K. , Kishnani Priya , Muenzer Joseph , Wenstrup Richard J. , Summar Marshall L. , Brummond Michael R. , Lachiewicz Ave M. , Millington David S. , Kahler Stephen G.
Published: June 2005

Five patients presenting with non‐ketotic hyperglycinemia in the neonatal period were treated with sodium benzoate to normalize plasma glycine levels. This therapy resulted in seizure reduction and a marked increase in wakefulness. Plasma carnitine deficiency was noted in three of four patients tested, and benzoylcarnitine was identified in plasma, urine, and CSF. Treatment with L‐carnitine normalized plasma free carnitine. L‐carnitine showed a tendency to increase the glycine conjugation of benzoate. An episode of coma and increased seizures in one patient was associated with a toxic level of benzoate, probably due to insufficient mobilization of glycine for conjugation. High dose benzoate therapy improved the quality of life of surviving patients. Close monitoring of glycine, benzoate and carnitine levels is advised. © 1995 Wiley‐Liss, Inc.
Crossover analysis in a British family suggests that Coffin‐Lowry syndrome maps to a 3.4‐cM interval in Xp22
Authors: Bird Helen , Collins Amanda L. , Oley Christine , Lindsay Susan
Published: June 2005

Coffin‐Lowry syndrome (CLS; MIM 303600) is an uncommon X‐linked disorder causing mental retardation and skeletal abnormalities. Most recently it was mapped to a 5.6‐centimorgan (cM) region of Xp22, flanked distally by AFM291 wf5 and proximally by DXS1052 [Biancalana et al., 1994: Genomics 22:617–625]. We present information which supports this localization and further narrows the region to approximately 3.4 cM. A recombination in a carrier from a British family means that DXS365 is the closest proximal flanking marker identified to date for the region thought to contain the CLS gene. This information reduces the region of interest by approximately 2.2 cM, a significant decrease in terms of the scale of effort which will be required to isolate and analyze candidate genes. © 1995 Wiley‐Liss, Inc.
Deletion of the entire NF1 gene detected by FISH: Four deletion patients associated with severe manifestations
Authors: Wu Bai‐Lin , Austin Michele A. , Schneider Gretchen H. , Boles Richard G. , Korf Bruce R.
Published: June 2005

Genetic analysis of NF1 has indicated a wide diversity of mutations, including chromosome rearrangements, deletions, insertions, duplications, and point mutations. Recently, five severely affected individuals have been found by Kayes et al. [1994] to have deletions encompassing the entire gene. These deletions were detected by quantitative Southern analysis. To simplify deletion detection, we have employed fluorescence in situ hybridization (FISH) using intragenic probes. Thirteen unrelated individuals with NF1 have been studied. Among six with severe manifestations, four have been found to have deletions detected by probes cFF13, cFB5D, cP5, yA43A9, yA113D7 and yD8F4. All four deletion patients have severe developmental delay, minor and major anomalies (including one with bilateral iris colobomas), and multiple cutaneous neurofibromas or plexiform neurofibromas which were present before age 5 years. FISH provides a simple and rapid means of identification of NF1 gene deletions and will allow more rigorous testing of the hypothesis that such deletions are associated with severe manifestations. © 1995 Wiley‐Liss, Inc.
Evidence that the APOE locus influences rate of disease progression in late onset familial Alzheimer's Disease but is not causative
Authors: Bennett Craig , Crawford Fiona , Osborne Aaron , Diaz Patricia , Hoyne Jonathan , Lopez Robert , Roques Penelope , Duara Ranjan , Rossor Martin , Mullan Mike
Published: June 2005

An association has been observed in several independent data sets between late onset Alzheimer's Disease (AD) and the APOE locus on chromosome 19. We have examined the genotype in family history positive (FHP) and family history negative (FHN) cases and find a distortion of the APOE allele frequencies in accord with previous studies. However, when we examined the allele distribution of the at‐risk siblings of the FHP group we found an excess of the ϵ4 allele which also differs significantly from historic controls but not from the affected siblings. The age distribution of the affected and unaffected siblings was similar, suggesting that the allelic frequency distortion in the unaffected siblings was not due to their being below the mean age of onset. Lod score linkage analysis, with age dependent onset and non‐stringent specification of the genetic parameters, did not suggest linkage to the APOE locus. Furthermore, an analysis of variance of the age of disease free survival suggested that APOE genotype contributes a small fraction of the total variance indicating that the APOE locus is a poor predictor of disease free survival age within late onset families. One explanation for the age dependent association reported by other groups, and our results, is that the APOE locus enhances the rate of progression of the disease process in otherwise predisposed individuals and that variation at this locus is not able in and of itself to cause the disease. We suggest this hypothesis is compatible with the current literature regarding APOE and AD. © 1995 Wiley‐Liss, Inc.
Autism, affective disorders, and social phobia
Authors: Smalley Susan L. , McCracken James , Tanguay Peter
Published: June 2005

The purpose of this study is to test the hypothesis that major affective and/or anxiety disorders are increased among relatives of autistic probands compared with controls. Among 36 families with an autistic child, 23 (64%) have a first degree relative diagnosed with major depressive disorder and 14 (39%) have a first degree relative diagnosed with social phobia. These rates are significantly greater than the 19% and 5%, respectively, found among 21 families with a child having a genetic condition, tuberous sclerosis complex, or a seizure disorder but no autism. The frequency of major depression among the 96 first degree relatives of autistic probands is 37.5% compared with 11.1% found among 45 relatives of control probands. The frequency of social phobia, 20.2%, is approximately 10 times more common than that found among the relatives of the control probands (2.4%). Elevated rates of both major depression and social phobia are found among parents and siblings in the families with an autistic child. Furthermore, 64% of parents affected with a major depression had the onset of the first depressive episode prior to the birth of the autistic child and all parents with social phobia had the onset of condition prior to the birth of the autistic child.

Family patterns differ depending on the intellectual level of the autistic child; specifically, social phobia is significantly greater among the first degree relatives of nonretarded autistic probands than among relatives of individuals with autism and comorbid mental retardation. Whether this familial association of autism, major mood disorders, and social phobia reflects shared genetic underpinnings requires further research. © 1995 Wiley‐Liss, Inc.
Word‐finding difficulties, verbal paraphasias, and verbal dyspraxia in ten individuals with fragile x syndrome
Authors: Spinelli Mauro , Rocha Ana Clelia De Oliveira , Giacheti Celia Maria , Richieri‐Costa A.
Published: June 2005

Speech/language disorders are common in the fragile X syndrome. [Howard‐Peebles, 1979: Am J Hom Genet 31:214–222; Renier et al., 1983: J Ment Defic Res 27:51–59; Sparks, 1984: Birth Defects and Speech‐Language Disorders, pp. 39–43; Hanson et al., 1986: Am J Med Genet 23:195–206]. Verbal paraphasias have been considered a rare feature and word‐finding difficulties have seldom been reported. Here we report on ten Brazilian patients who were evaluated for speech/language disturbances and found that word‐finding difficulties were present in 50% of the cases, which is a slightly higher frequency than that of clear dyspraxia. We suggest, therefore, that word‐finding difficulties and verbal dyspraxia can be a common feature within the spectrum of this syndrome. Additional speech findings are discussed. © 1995 Wiley‐Liss, Inc.
Exclusion of linkage between alcoholism and the MNS blood group region on chromosome 4q in multiplex families
Authors: Neiswanger Katherine , Kaplan Barry , Hill Shirley Y.
Published: June 2005

Polymorphic DNA markers on the long arm of chromosome 4 were used to examine linkage to alcoholism in 20 multiplex pedigrees. Fifteen loci were determined for 124 individuals. Lod scores were calculated assuming both dominant and recessive disease modes of inheritance, utilizing incidence data by age and gender that allow for correction for variable age of onset and frequency of the disorder by gender. Under the assumption that alcoholism is homogeneous in this set of pedigrees, and that a recessive mode with age and gender correction is the most appropriate, the total lod scores for all families combined were uniformly lower than −2.0. This suggests an absence of linkage between the putative alcoholism susceptibility gene and markers in the region of the MNS blood group (4q28—31), a region for which we had previously found suggestive evidence of linkage to alcoholism. The 100 cM span of chromosome 4 studied includes the class I alcohol dehydrogenase (ADH) loci. Using the recessive mode, no evidence for linkage to alcoholism was found for the markers tested, which spanned almost the entire long arm of chromosome 4. Under the dominant mode, no evidence for linkage could be found for several of the markers. © 1995 Wiley‐Liss, Inc.