bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular study of 45,X conceptuses: Correlation with clinical findings
Authors: Lorda‐Sanchez Isabel , Binkert Franz , Maechler Marco , Schinzel Albert
Published: June 2005

The parental origin of the single X in 45 cases (40 liveborns and 5 fetuses) with a 45, X karyo‐type was studied using polymorphic DNA probes. The single X was paternal in origin (Xp) in 10 cases (22.2%) and maternal (Xm) in 35 cases (77.8%). Y chromosome material was detected in 1 out of the 35 cases with a 45, Xm constitution. Analysis of parental ages and clinical data of the patients with respect to the origin of the single X revealed no significant differences between the origins.
Linkage map of the chromosomal region surrounding the infantile neuronal ceroid lipofuscinosis on 1p
Authors: Järvelä Irma , Santavuori Pirkko , Puhakka Lea , Haltia Matti , Peltonen Leena
Published: June 2005

The neuronal ceroid lipofuscinoses (NCLs) of childhood are divided into 3 main types according to age‐of‐onset, clinical course, and neurophysiological and neuropathological findings: infantile, late infantile, and juvenile. All forms are inherited as an autosomal recessive trait, and their biochemical background is still unknown. The infantile type (INCL) with the earliest age‐of‐onset and the most severe clinical course, occurs in Finland with an incidence of 1:20,000, i.e., 116 patients have been found in our country up to now, whereas only about 50 cases have been reported from other parts of the world.

Earlier we reported the linkage of INCL to the short arm of chromosome 1. Here we describe a more precise linkage map of this area. Our current map places the INCL mutation between D1S57 and D1S79; D1S7 has so far shown no recombination events between the marker and the disease (lod score 4.55 at θ = 0.00). Our material includes 64% of all living patients in Finland, and no linkage disequilibrium of haplotypes is seen, using the 2 physically close markers D1S57 and D1S79. This finding as well as our LINKMAP analyses suggest that the distance between the disease locus and the flanking markers is about 3–4 cm.
Evidence for processing of dolichol‐linked oligosaccharides in patients with neuronal ceroid‐lipofuscinosis
Authors: Daniel Peter F. , Sauls Derrick L. , Boustany Rose‐Mary N.
Published: June 2005

In agreement with reports from other laboratories, we have shown that patients with the juvenile or late infantile forms of neuronal ceroid‐lipofuscinosis (NCL) have greatly increased levels (5‐fold to 20‐fold) of dolichyl pyrophosphoryl oligosaccharides in their cerebral gray matter. Oligosaccharides cont ain‐ing 2 GlcNAc residues and 3 to 9 mannose residues were liberated by mild acid hydrolysis. The oligosaccharide profile given by brain tissue from 2 patients with infantil e NCL was markedly different from that of late infantile and juvenile NCL brain, with Man9GlcNAc2 as the most abundant component and decreasing amounts of Man8‐ Man7‐and Man6GlcNAc2. By contrast, Man5GlcNAc2 was the most abundant oligosaccharide present in all juvenile NCL brain samples analyzed. Both the susceptibility of the isolated Man5GlcNAc2 to endoglucosaminidase H digestion and permethylation analysis clearly indicated that it is not an intermediate in the biosynthesis of Glc3Man9GlcNAc2‐PP‐dolichol but has undergone catabolism, probably either in the endoplasmic reticulum or in the Golgi apparatus. Treatment of cultured skin fibroblasts for 7 days with N‐methyldeoxyno‐jirimycin, a potent inhibitor of the endoplasmic reticulum processing enzymes glucosidase I and II, resulted in an accumulation of the same Man5GlcNAc2‐PP‐dolichol species that was elevated in juvenile NCL brain. The level in untreated fibroblasts was undetectable, suggesting that inhibition of processing glu‐ cosidases has interfered with the regulation and compartmentalization of lipid‐linked oli‐gosaccharides.
Niemann‐Pick type‐C disease: Deficient intracellular transport of exogenously derived cholesterol
Authors: Roff Calvin F. , Goldin Ehud , Comly Marcella E. , Blanchette‐Mackie Joan , Cooney Adele , Brady Roscoe O. , Pentchev Peter G.
Published: June 2005

NPC disease is an autosomal recessive neurovisceral storage disorder. A pleiotropic array of secondary enzymatic and storage abnormalities has in the past obscured a cohesive understanding of the underlying metabolic basis of this disorder. Recent findings, reviewed in this report, demonstrate that NPC disease is a cholesterol lipidosis resulting from defective intracellular cholesterol transport. The sequence of cellular events characteristic of NPC is 1) deficient intracellular transport of exogenously derived cholesterol resulting in retarded induction of cellular cholesterol homeostatic regulation; 2) accumulation of cholesterol, in lysosomes; and 3) secondary cellular effects. Retarded esterification of exogenous cholesterol and accumulation of unesterified cholesterol in lysosomes is tightly coupled to the primary defect and serves as the basis for biochemical diagnosis of NPC.
Retina in various animal models of neuronal ceroid‐lipofuscinosis
Authors: Goebel Hans H.
Published: June 2005

The childhood forms of human neuronal ceroid‐lipofuscinosis (NCL) are invariably associated with a severe progressive retinopathy which commences at the photoreceptor level morphologically and proceeds to a final loss of neuronal cells accompanied by severe gliosis. In respective spontaneous animal conditions of NCL, in English setters, Dalmatian dogs, and New Zealand sheep, retinal involvement is not commensurate although the retina does not seem to be completely unaffected. In canine NCL, there might be functional and electro‐physiological impairment of retinal cells, but retinal atrophy is not obvious. In ovine NCL, the retina, apart from accumulating NCL‐specific lipopigments within neuronal perikarya, also shows loss of photoreceptors. Conversely, retinal pigment epithelial cells (RPE) in canine and ovine NCL contain peculiar lamellar inclusions, not seen in unaffected animals, possibly an indication of a disturbed phagocytic process of photoreceptor outer segments. Similar such lamellar inclusions have not been observed in RPE cells in human childhood NCL.
Mucopolysaccharidosis VII as cause of fetal hydrops in early pregnancy
Authors: Stangenberg Magnus , Lingman Göran , Roberts George , Ozand Pinar
Published: June 2005

We report on fetal hydrops presenting at 18 weeks of gestation and diagnosed as β‐glucuronidase deficiency. The parents were first cousins and there were 2 previous similar fetal deaths. β‐Glucuronidase was absent in cultured fetal fibroblasts and lymphoblasts but was normal in the tested relatives. The activities of other lysosomal enzymes were normal. © 1992 Wiley‐Liss, Inc.
Autosomal recessive cleft lip/palate, ectodermal dysplasia, and minor acral anomalies: Report of a Brazilian family
Authors: Richieri‐Costa Antonio , Guion‐Almeida Maria Leine , Freire‐Maia Newton , Pinheiro Marta
Published: June 2005

We report on a Brazilian woman, born to consanguineous (first cousin) parents (F = 1/16) and presenting cleft lip/palate, ectodermal dysplasia, interdigital webbing, and other malformations. Parental consanguinity and possible recurrence in sibs suggest autosomal recessive inheritance. The nosologic aspects with the Martinez syndrome and with the Zlotogora–Ogur syndrome are discussed. © 1992 Wiley‐Liss, Inc.
Constitutional translocation t(4;22) (q12;q12.2) associated with neurofibromatosis type 2
Authors: Arai Eiko , Ikeuchi Tatsuro , Karasawa Shinji , Tamura Akira , Yamamoto Kohtaro , Kida Mitsushiro , Ichimura Koichi , Yuasa Yasuhito , Tonomura Akira
Published: June 2005

We report on a female patient with bilateral acoustic neurinomas and other tumors in the central nervous system (neurofibromatosis type 2: NF2) and the constitutional translocation, t(4;22) (q12;q12.2). The precise identification of the translocation breakpoint (q12.2) on chromosome 22 implies the refined localization of a gene responsible for NF2, and would provide a clue to its molecular characterization and to the isolation of the gene. Chromosomes of a paraspinal neurinoma from the patient were also analyzed, and the same karyotype as seen in cultured peripheral lymphocytes was found. The patient's father was also a carrier of the translocation, but he had no clinical symptoms of NF2, nor did other relatives. Several explanations are offered for the different expression of the translocation between the patient and her father. © 1992 Wiley‐Liss, Inc.
Twin studies in familial mediterranean fever
Authors: Shohat M. , Livneh A. , Zemer D. , Pras M. , Sohar E.
Published: June 2005

Familial Mediterranean fever (FMF) is a genetic disease characterized by recurrent short episodes of fever, accompanied by peritonitis, pleuritis, or arthritis. The disease is almost completely ethnically restricted to patients of Mediterranean descent—Sephardic Jews, Armenians, Anatolian Turks, and Arabs. Although many family studies have been performed, no twin study has been reported as yet. We studied 21 di‐ and monozygotic twin sets, identified among the 1,943 FMF patients in our registry. Full concordance was observed in all the 10 monozygotic twin sets. In the 11 dizygotic twins, concordance for FMF disease was found in only 3 pairs. Variability in the clinical manifestations and degree of severity have been noted within twins. These findings provide definitive evidence for the genetic cause of FMF. They also support the single gene autosomal recessive model, and provide support for the contention that the lower observed than expected incidence found in FMF is due to genetically affected but clinically undiagnosed patients. © 1992 Wiley‐Liss, Inc.
Familial mediterranean fever: Analysis of inheritance and current linkage data
Authors: Shohat Mordechai , Danon Yehuda L. , Rotter Jerome I.
Published: June 2005

Familial Mediterranean fever (FMF) is a genetic disorder characterized by recurrent attacks of fever and inflammation of serosal surfaces. Unlike many mendelian disorders, the mode of transmission has been subject to some controversy as segregation analysis studies have always demonstrated fewer “observed” than “expected” affected individuals. Despite efforts to map the gene causing FMF, no definite linkage has been yet identified. This review analyses the epidemiologic and genetic characteristics in order to evaluate critically the inheritance of the disease and provide a perspective on the current biochemical and molecular genetic studies whose aim is to locate the gene for this disease. © 1992 Wiley‐Liss, Inc.
Natural history of mosaic trisomy 14 syndrome
Authors: Fujimoto Atsuko , Allanson Judith , Crowe Carol A. , Lipson Mark H. , Johnson Virginia P.
Published: June 2005

Trisomy 14 mosaicism produces a distinct phenotype. Among the 13 reported and 2 additional patients, the following findings were present in more than 90%: growth retardation (15/15), psychomotor retardation (10/10), broad nose (13/14), “dysplastic” and/or apparently low‐set ears (15/15), micrognathia (15/15), short neck (11/12), congenital heart disease (14/15), and micropenis and cryptorchidism (6/6). Other frequent findings were prominent forehead (12/14), hypertelorism (8/13), narrow palpebral fissure (7/9), large mouth (10/14), cleft or highly arched palate (10/14), body asymmetry (8/12), and abnormal skin pigmentation (6/10). Sex ratio was 6M:9F. Four patients died before age 4 months, while at least 2 patients survived through teens. One boy died at age 3 years following cardiac surgery. One girl with tetralogy of Fallot showed a remarkable improvement in health after Blalock–Taussig procedure. Although the surviving patients showed moderate growth and mental retardation, the oldest surviving woman at 29 years demonstrates functional language and appropriate self help skills. © 1992 Wiley‐Liss, Inc.
Hypoplasia of the corpus callosum and growth hormone deficiency in the XXXXY syndrome
Authors: Haeusler Gabriele , Frisch H. , Guchev Z. , Hadziselimovic F. , Neuhold A. , Vormittag W.
Published: June 2005

A 3‐year‐old Libyan boy with the XXXXY syndrome is described. MRI examination of the brain showed hypoplasia of the corpus callosum. He had growth retardation and endocrine studies demonstrated growth hormone (GH) deficiency. Dermatoglyphic pattern was different from previous reports. At histological examination of the undescended testes, Leydig cells were seen although they are usually not found in this variant of the Klinefelter syndrome. © 1992 Wiley‐Liss, Inc.
Child with manifestations of dermotrichic syndrome and ichthyosis follicularis‐alopecia‐photophobia (IFAP) syndrome
Authors: Martino F. , D'Eufemia P. , Pergola M. S. , Finocchiaro R. , Celli M. , Giampà G. , Frontali M. , Giardini O.
Published: June 2005

We report on a boy with short stature, mental retardation, seizures, follicular ichthyosis, generalized alopecia, hypohydrosis, enamel dysplasia, photophobia, congenital aganglionic megacolon, inguinal hernia, vertebral, renal and other anomalies, and a normal chromosome constitution. The clinical findings include all the features that dermotrichic and ichthyosis follicularis‐alopecia‐photophobia (IFAP) syndrome have in common and in addition those that characterize IFAP syndrome (photophobia, recurrent respiratory infections, etc.), those that are present only in dermotrichic syndrome (nail anomalies, hypohydrosis, megacolon, vertebral defects, etc.) and additional ones (enamel dysplasia, renal anomalies, inguinal hernia, etc.). Two maternal uncles were referred as being affected by alopecia and ichthyosis suggesting X‐linked recessive transmission. Various hypotheses concerning the relationship between the 2 syndromes and the present case are discussed © 1992 Wiley‐Liss, Inc.
Amniotic band sequence: Streeter's hypothesis reexamined
Authors: Bamforth J. Stephen
Published: June 2005

Recently published reports of 54 subjects with the amniotic band syndrome (ABS) were reviewed, paying particular attention to internal anomalies. Evidence from the internal anomalies suggests that in most cases reviewed, damage occurred in a definable time period, probably prior to 26 days postconception and before the establishment of effective embryonic circulation. Most defects are explicable in terms of interference with neuropore closure, malmigration of cephalic neural crest tissue, and damage to the mesonephros consistent with local interference of the graded expression of organizational genes resulting in a local defect in the organization of the embryo. © Wiley‐Liss, Inc.
Sling left pulmonary artery, bridging bronchus, and associated anomalies
Authors: Medina‐Escobedo Gilberto , Lopez‐Corella Eduardo
Published: June 2005

Sling left pulmonary artery (SLPA) is often associated with tracheobronchial abnormalities, including bridging bronchus (BB). We report on 3 patients with SLPA: One patient had a narrow trachea, absent right upper lobe and right main bronchus, and BB. The second patient had a long and narrow trachea, with normal segmentation of bronchial tree, abnormal cerebral gyri, and minor facial abnormalities. The third patient, with a normal trachea and main bronchi with BB, had imperforate anus, hemivertebrae, and atrial septal defect (VATER association). Patients with SLPA, those with BB, or those with both SLPA and BB as well as multiple congenital anomalies represent a spectrum of anomalies. © Wiley‐Liss, Inc.
Fluorescence in situ hybridization (FISH) of a whole‐arm translocation involving chromosomes 18 and 20 with α‐satellite DNA probes: Detection of a centromeric DNA break?
Authors: Cantú Eduardo S. , Khan Tasneem A. , Pai G. Shashidhar
Published: June 2005

Fluorescence in situ hybridization (FISH) with α‐satellite DNA probes was used to study whole‐arm chromosome translocation products in a family in which the propositus was shown to have a monosomy 18p/trisomy 20p imbalance. By this approach, we show that the chromosome 18 α‐satellite DNA block is split into 2 smaller units, whereas the chromosome 20 breakpoint is not included within the α‐satellite DNA region. We found no evidence to suggest that this split α‐satellite DNA region has reduced or impaired the function of the centromere or that it contributed to the phenotype of the propositus. The FISH technique critically demonstrated the involvement of a whole‐arm translocation in this case and provided accurate identification of breakpoints, which was not possible with standard banding techniques. © Wiley‐Liss, Inc.
Triply discordant triplets: Probability, management options, and risks
Authors: Pryde Peter G. , Isada Nelson B. , Johnson Mark P. , Grundy Howard , Evans Mark I.
Published: June 2005

The spontaneous occurrence of triplets is rare. With increased utilization of “assisted reproductive technologies,” multifetal gestations have become more common. The empiric fetal risk for major malformation is ∼ 3%. In a triplet pregnancy each fetus independently carries this risk so that the probability of having at least one malformed fetus is ∼ 9%. It is much less likely to have 2 or 3 simultaneously but discordantly malformed fetuses in a multizygotic triplet gestation (.09% and .0027% risk, respectively). We report on the first case, to our knowledge, of an ovulation‐stimulated triplet pregnancy complicated by 3‐way discordance for major malformations diagnosed in the late second trimester by ultrasound. Fetus A was affected by congenital diaphragmatic hernia and trisomy 21; fetus B had encephalocele, a midline facial defect, and a cleft palate; and fetus C had evidence of unilateral claw hand but an otherwise normal fetal survey. At 19 weeks of gestation, fetus A was found to have spontaneously died, and a selective termination of triplet B was performed. We conclude: (1) the finding of a single major malformation in one fetus should lead to extensive search for malformations in all members of the pregnancy, and (2) the simultaneous occurrence of major malformations in more than one member of a multifetal gestation is a circumstance under which multiple selective termination deserves consideration. In this article we discuss important issues and caveats in the performance of selective termination for abnormal members of multifetal gestations. © Wiley‐Liss, Inc.
Ectodermal dysplasia, lipoatrophy, diabetes mellitus, and amastia: A second case of the AREDYLD syndrome
Authors: Breslau‐Siderius E. J. , Toonstra J. , Baart J. A. , Koppeschaar H. P. F. , Maassen J. A. , Beemer F. A.
Published: June 2005

A 19‐year‐old female with ectodermal dysplasia, lipoatrophy, diabetes mellitus, and amastia is described. This complex of symptoms is very similar to that of a case published by Pinheiro et al [1983] under the acronym of AREDYLD syndrome. © Wiley‐Liss, Inc.
Additional dystrophin fragment in Becker muscular dystrophy may result from proteolytic cleavage at deletion junctions
Authors: Beggs Alan H. , Hoffman Eric P. , Kunkel Louis M.
Published: June 2005

Becker muscular dystrophy is usually caused by intragenic dystrophin gene deletions that result in production of an internally deleted protein. Previous studies have detected what appears to be a unique dystrophin degradation product that appears only in muscle biopsies from patients with Becker muscular dystrophy. This dystrophin fragment is always seen in addition to the “full‐size” dystrophin of the expected size for a given gene deletion. It is only found in biopsies from patients with mutations in the deletion‐prone region encompassing exons 45–53, but it does not appear to correlate with any observable phenotype at the clinical level. By correlating the size and locations of dystrophin gene deletions with the size of this degradation product, together with use of region‐specific dystrophin antisera, we find that proteolytic cleavage may occur at the deletion breakpoints, perhaps due to alterations of the secondary and/or tertiary structures of the protein. This cleavage results in loss of the carboxy‐terminal domains that are thought to be important for interactions between dystrophin and other membrane‐bound proteins. © Wiley‐Liss, Inc.
Uncultured blood smears hybridized with alpha satellite probes to diagnose 45,X in spontaneously aborted fetuses
Authors: von Kap‐herr C. , Kelly Thaddeus E. , Golden Wendy L.
Published: June 2005

Traditional cytogenetic analysis of material from spontaneous abortions often fails due to non‐viability of the tissues in cell culture. The 45,X constitution is common in early pregnancy loss. Fluorescent in situ hybridization (FISH) was used to diagnose 45,X in uncultured blood smears obtained from 2 cases of spontaneous pregnancy loss with fetal hydrops. The ability of chromosome specific alpha satellite probes to detect aneuploidy in uncultured cells should greatly increase the successful detection of chromosomal abnormalities in early abortuses.
Study of the etiology of deafness in an institutionalized population in colombia
Authors: Tamayo Marta L. , Bernal Jaime E. , Tamayo Gustavo E. , Frias Jaime L.
Published: June 2005

To identify causative factors we screened 1,715 deaf individuals from 16 schools for the deaf in Colombia. We found evidence of environmental causation in 579 (33.8%) cases, genetic in 608 (35.4%), and in 528 (30.8%) we were unable to identify the etiology. The degree of hearing loss was severe to profound in 1,238 (72.2%), although in 987 (57.5%) of the deaf population studied the hearing impairment was not noticed until 2 to 5 years of age.

The frequent association of deafness with other anomalies underscores the importance of a careful clinical and ophthalmologic evaluation in individuals with hearing loss. Our observations also emphasize the need for programs directed towards the prevention of hearing loss, including primary prevention as well as early diagnosis, investigation of possible genetic causes, and rehabilitation of deaf individuals.
Elevated second trimester maternal serum β‐HCG concentrations and subsequent adverse pregnancy outcome
Authors: Gravett Claudia P. , Buckmaster John G. , Watson Peter T. , Gravett Michael G.
Published: June 2005

Previous studies have found an association between elevated second trimester maternal serum α‐fetoprotein (MS‐AFP), in the absence of fetal anomalies, and adverse pregnancy outcome. We studied the association between elevated second trimester maternal serum β‐HCG, now also routinely measured by prenatal screening programs, and adverse pregnancy outcome by reviewing retrospectively the pregnancy outcomes among women with markedly elevated midtrimester β‐HCG in our prenatal screening program. Seven (0.23%) of 3,000 consecutively screened women had a serum β‐HCG above 5 MOM. Four (57%) of these 7 women had an adverse pregnancy outcome including severe preeclampsia (n = 2), abruptio placentae (n = 1), or preterm labor (n = 1). A concurrently elevated MS‐AFP was found in only one of these 4 patients. Elevated midtrimester maternal serum β‐HCG may be an independent risk factor for subsequent adverse pregnancy outcomes.
Deletion of the KIT and PDGFRA genes in a patient with piebaldism
Authors: Spritz Richard A. , Droetto Sara , Fukushima Yoshimitsu
Published: June 2005

We have previously shown that human piebaldism results from mutations of the KIT gene, which encodes the receptor for the mast/stem cell growth factor and is located in chromosome segment 4q12. Using DNA of a patient with piebaldism, mental retardation, and multiple congenital anomalies associated with a 46,XY,del(4) (q12q21.1) karyotype, we carried out quantitative Southern blot hybridization analyses of the KIT gene and the adjacent PDGFRA (platelet‐derived growth factor receptor α subunit) genes. The patient was hemizygous for both the KIT and PDGFRA genes, indicating that both of these genes are included within the deleted region. Therefore, deletion of the KIT and PDGFRA genes may account for the piebald phenotype in this patient.© Wiley‐Liss, Inc.
Hepatoerythropoietic porphyria in a woman with short stature and deformed hands
Authors: Fujimoto Atsuko , Brazil James L.
Published: June 2005

A 23‐year‐old woman from Honduras was diagnosed to have hepatoerythropoietic porphyria. She had photosensitive skin of early onset, hypertrichosis, and severe scleroderma‐like lesions of the hands. Erythrocyte uropor‐phyrinogen decarboxylase activity was reduced to about 10% of the normal activity. © Wiley‐Liss, Inc.
Smallest terminal deletion of the long arm of chromosome 2 in a mildly affected boy
Authors: Lin Shuan‐Pei , Petty Elizabeth M. , Gibson Lisa H. , Inserra Joann , Seashore Margretta R. , Yang‐Feng Teresa L.
Published: June 2005

We describe a male twin with the smallest terminal deletion of chromosome 2q [46,XY,del(2)(q37.2)] reported to date. His deletion was confirmed by a fluorescence in situ hybridization study using a probe from the deleted region. Only 3 other cases with larger deletions including 2q37.2→qter have been reported. Clinical manifestations our patient has in common with them include frontal bossing, long eyelashes, micrognathia, infantile hypotonia and developmental delay. His twin brother is physically and developmentally normal and chromosomes of the parents were normal. The mildness of the phenotype in this patient supports less stringent criteria for cytogenetic study of developmentally impaired individuals. © Wiley‐Liss, Inc.
Parental sex effect in spina bifida: A role for genomic imprinting?
Authors: Chatkupt Sansnee , Lucek Paul R. , Koenigsberger M. Richard , Johnson William G.
Published: June 2005

Fifty families (491 individuals in 137 sibships) with more than one living case of isolated, nonsyndromic spina bifida (SB) were analyzed genetically. There were twice as many gene‐carrier females (56) as gene‐carrier males (28) (P < 0.005). This was not an artifact of ascertainment bias because the sex ratio of gene‐carriers was the same whether the pedigree was obtained through the proband's father or mother. Also, this effect was not observed in other disorders analyzed by the same method. Neither was the effect due to differential fertility because the number and sex of affected and unaffected children per gene‐carrier parent were not different for male or female gene‐carrier parents. There was no evidence that the missing male gene‐carriers were lost by selective spontaneous abortion. There was no deficit of male‐to‐male or male‐to‐female transmission, excluding simple X‐linked or simple mitochondrial inheritance. If genomic imprinting plays a role in the unequal female and male carrier frequencies in SB, penetrance should differ with parental sex. Penetrance was higher for off‐spring of female parents than of male parents, but the difference was not statistically significant. In addition, both male and female gene‐carriers were frequently found in the same pedigree. Thus, the present data suggest a possible role for imprinting in SB. © Wiley‐Liss, Inc.
Autosomal recessive oral‐facial‐digital syndrome with resemblance to OFD types II, III, IV and VI: A new OFD syndrome?
Authors: Chitayat David , Stalker Heather J. , Azouz E. Michael
Published: June 2005

We report on a son and daughter of Ashkenazi‐Jewish parents with postaxial polydactyly of the hands and feet associated with syndactyly and brachydactyly, mental retardation, cerebellar hypoplasia, pectus excavatum, mesomelic shortness of the upper and lower limbs, and pretibial dimples. Although this appears to be an example of one of the OFD syndromes and has many similarities to OFD type II,III,IV and VI, it does not fit satisfactorily into any of the types previously described. Thus this may be a new OFD syndrome, although we cannot exclude a possibility that most or all autosomal recessive OFD syndromes are the result of pleiotropy of a single mutation in a homozygous state. © 1992 Wiley‐Liss, Inc.
Predictions of a 2‐locus model for disease heterogeneity: Application to adrenoleukodystrophy
Authors: Maestri N. E. , Beaty T. H.
Published: June 2005

Adrenoleukodystrophy (ALD) is an X‐linked disorder that exhibits a wide range of phenotypic variability within individuals in a single family carrying the mutant allele. A 2‐locus epistatic model has been proposed to explain the inheritance of the severe childhood form of ALD and the milder adult‐onset adrenomyloneuropathy (AMN). Under a dominant epistatic model, a single M allele at an autosomal modifier locus ameliorates the most severe effects of the disease allele leading to the milder AMN phenotype; only males with genotype mm would have ALD. Under a recessive epistatic model, 2 copies of the M allele would be necessary to have the milder AMN phenotype. Here, we show that recurrence risks for a second affected male depend on the frequency of the protective allele at this modifier locus. Whereas it is most likely that 2 affected brothers will be concordant for their disease phenotypes, discordant pairs of affected brothers are possible at all frequencies of M. Within a narrow range of modifier allele frequencies, the predicted distribution of affected sib pairs (over all families) is consistent with empiric data from a large clinic population. Here we suggest sampling discordant affected sib pairs as a strategy for detecting linkage between a polymorphic DNA marker and a possible modifier gene. Since both epistatic models predict that discordant affected pairs should not share 2 alleles at the modifier locus, we expect that departures from the null distribution could be detected with relatively small numbers of sib pairs. © 1992 Wiley‐Liss, Inc.
Familial omphalocele: Considerations in genetic counseling
Authors: Pryde Peter G. , Greb Anne , Isada Nelson B. , Johnson Mark B. , Klein Michael , Evans Mark I.
Published: June 2005

Nonsyndromal omphalocele is generally regarded as a sporadic malformation. Recurrence risk is considered negligible. We report on a patient in whom 5 consecutive pregnancies (by 2 separate nonconsanguineous partners) were complicated by omphalocele as an isolated defect. Neither the patient nor her partners had history of relatives with omphalocele, although the patient's brother and his son had large umbilical hernias requiring repair in infancy. Some familial cases of nonsyndromal omphalocele have been previously reported; most such pedigrees suggest vertical transmission, although there are a few cases with only a single generation involved. In Our case, the multigenerational finding of ventral wall hernias makes an autosomal dominant mechanism with variable expressivity a tenable explanation. The collected instances of familial nonsyndromal omphalocele emphasize omphalocele heterogeneity and caution in counseling recurrence risks. © 1992 Wiley‐Liss, Inc.
Pseudo‐trisomy 13 syndrome with upper limb shortness and radial hypoplasia
Authors: Boles Richard G. , Teebi Ahmad S. , Neilson Kathryn A. , Meyn M. Stephen
Published: June 2005

We report on a fetus with holoprosencephaly, postaxial polydactyly, multiple visceral anomalies, upper limb shortness, and radial hypoplasia with normal chromosomes. We provide a brief review of the newly delineated “pseudo‐trisomy 13 syndrome.” Severe limb shortness of radial hypoplasia has not been described previously in this syndrome. The present case may expand the spectrum of the pseudo‐trisomy 13 syndrome, or may represent a distinct entity. © 1992 Wiley‐Liss, Inc.
Spondylometaphyseal dysplasia, sedaghatian type
Authors: Peeden J. N. , Rimoin D. L. , Lachman R. S. , Dyer M. L. , Gerard D. , Gruber H. E.
Published: June 2005

In 1980 Sedaghatian described an Iranian infant who died shortly after birth. At autopsy, he was found to have subacute myocarditis, cortical necrosis of kidneys, and adrenal and pulmonary hemorrhage. His skeletal abnormalities included mild rhizomelic shortness of his limbs and platyspondyly and “laciness” of the iliac wings. In 1987 Opitz et al. described another Iranian infant with a similar perinatal course and roentgenograms. This infant was born to first cousins, suggesting an autosomal recessive single gene defect. We report our findings of another infant with a lethal course. © 1992 Wiley‐Liss, Inc.
Genetic‐epidemiologic study of omphalocele and gastroschisis: Evidence for heterogeneity
Authors: Yang Ping , Beaty Terri H. , Khoury Muin J. , Chee Elsbeth , Stewart Walter , Gordis Leon
Published: June 2005

On the basis of clinical manifestations, epidemiologic characteristics, and the presence of additional malformations, omphalocele (OM) and gastroschisis (GA) are considered causally and pathogenetically distinct abdominal wall defects. More than 50% of infants with OM have additional defects, but only about 15% of those with GA do. To evaluate whether there is heterogeneity between isolated and multiply affected cases of OM and GA, we analyzed epidemiologic characteristics and familial risks of major defects for 82 OM and 81 GA cases drawn from a population‐based study in the Maryland‐Washington, DC‐Northern Virginia area and born from 1980 through June 1987. We examined year of birth, sex, race, and maternal age distributions after stratifying the infants into isolated and multiple defect groups. We found significant differences in maternal age between cases with isolated OM and GA, but not between cases with GA or OM who had other defects. Using regressive logistic models, we analyzed familial aggregation of birth defects among relatives of infants with OM and GA. An autosomal recessive model of inheritance was found to be the most parsimonious explanation for the families of infants with isolated OM or GA. However, for families of infants with multiple defects, a sporadic or nongenetic model fit best. These findings are not only useful for estimating familial risk of major birth defects, but they also suggest further heterogeneity of infants with OM and GA according to the presence of other malformations. © 1992 Wiley‐Liss, Inc.
Williams syndrome in adults
Authors: Lopez‐Rangel E. , Maurice M. , McGillivray B. , Friedman J. M.
Published: June 2005

There are few published reports of adults with Williams syndrome (WS). We have evaluated ten adult WS patients. The patients in our study were very variable in clinical presentation, ranging from severely affected patients with complicated medical histories to mildly affected patients who are generally in good health. Cardiovascular anomalies and hypertension were frequent.

Supravalvular aortic stenosis was seen in four patients, mitral valve prolapse in three, bicuspid aortic valve in one, valvular aortic stenosis in one, and pulmonary stenosis with right ventricular hypertrophy in one. Typical facial features included stellate irides, prominent cheeks, full lips, and micrognathia.

Mental retardation was seen in all patients. Verbal skills were better developed than motor skills. All patients in our study lead active lives, and most are involved in sports. Some hold supervised jobs. Eight of our patients live with their parents and two in group homes. Independent living is restricted by their mental and adaptive limitations. © 1992 Wiley‐Liss, Inc.
Type II collagen defect in two sibs with the Goldblatt syndrome, a chondrodysplasia with dentinogenesis imperfecta, and joint laxity
Authors: Bonaventure J. , Stanescu R. , Stanescu V. , Allain J. C. , Muriel M. P. , Ginisty D. , Maroteaux P.
Published: June 2005

We report on a syndrome of spondylo‐epimetaphyseal dysplasia, dentinogenesis imperfecta, and ligamentous hyperextensibility in two sibs born to nonconsanguineous parents. This chondrodysplasia was characterized by severe shortness of stature and an osteoporosis without fractures.

Electron microscopic examination of the cartilage documented large vacuoles of dilated rough endoplasmic reticulum within the cytoplasm of chondrocytes. Gel electrophoresis of pepsin‐soluble collagen extracted from cartilage demonstrated the presence of type II collagen chains with an abnormal mobility. Prolyl and lysyl hydroxylations were slightly increased. The abnormal molecules melted at a higher temperature than the normal ones. CNBr peptide mapping of type II collagen showed an altered electrophoretic migration of peptides CB 11, CB 8, and CB 10,5 whereas CB 9,7 looked normal. In addition, two small non‐collagenous proteins isolated from cartilage were not found in an age‐matched control individual but were detected in a normal newborn infant. The quantitation of proline‐labelled collagen synthesized by dermal fibroblasts demonstrated a 50% reduction of total collagen. This decrease essentially affected the amount of extracellular type I collagen, which was secreted less efficiently than in control cells. Nevertheless, type I collagen chains behaved normally on 5% polyacrylamide gels. The reduced mRNA levels of α1I and α2I chains might reflect either a transcriptional defect or a decreased stability of mRNA transcripts. We suggest that the association of both pathological chondrocytes producing altered collagen type II and decreased synthesis of type I could be responsible for this peculiar phenotype. The overmodification of α1II CNBr peptides is consistent with the presence of a single‐base substitution in the COL2A1 gene. Whether there is a direct causal relationship between the type II collagen defect and the underexpression of type I collagen will require clarification. © 1992 Wiley‐Liss, Inc.
Upper limb deficiencies and associated malformations: A population‐based study
Authors: Froster Ursula G. , Baird Patricia A.
Published: June 2005

As part of an ongoing analysis of limb deficiencies occurring among 1,213,913 consecutive livebirths in British Columbia during the years 1952–1984, all cases with deficiencies of the upper limbs were analysed with a view to identifying associated patterns of anomalies. This analysis resulted in seven subgroups. For each subgroup, incidence figures for cases with and without additional anomalies were calculated separately. The proportion of cases with additional anomalies varied markedly by subgroup. For example, 89% of cases with longitudinal defects of the radius had additional malformations, while only 28% of cases with transverse defects of the radius had other organ anomalies (χ2 = 40.55; P < 0.001, one degree of freedom). A preponderance of males was found among the cases with associated defects, particularly in the group with longitudinal defects of the radius (28 males, 14 females; χ2 = 14.10; P < 0.001). Clustering of specific patterns of associated malformations is described within subgroups. © 1992 Wiley‐Liss, Inc.
Tricho‐Rhino‐Phalangeal syndrome type II (Langer‐Giedion) with persistent cloaca and prune belly sequence in a girl with 8q interstitial deletion
Authors: Ramos Feliciano J. , McDonald‐McGinn Donna M. , Emanuel Beverly S. , Zackai Elaine H.
Published: June 2005

A patient with the diagnosis of Langer‐Giedion syndrome (tricho‐rhino‐phalangeal syndrome type II) and interstitial 8q deletion was also noted to have persistent cloaca and prune belly sequence. This is the first report of this association. If it postulated that these latter embryonic defects may be due to the chromosome abnormality, supporting the definition of contiguous gene syndrome. © 1992 Wiley‐Liss, Inc.
Urinary tract involvement in EEC syndrome: A clinical study in 25 Brazilian patients
Authors: Nardi Aguinaldo C. , Ferreira Ubirajara , Netto Nelson Rodrigues , Magna Luis Alberto , Rodini E. S. O. , Richieri‐Costa A.
Published: June 2005

We have evaluated 25 patients (14 isolated and 11 familial cases) with the EEC syndrome for genitourinary (GU) tract anomalies through intravenous pyelogram (IVP), voiding urethrocystography, and sonographic examination. Fifty‐two percent of the patients (7 isolated and 6 familial cases) had involvement of the urinary tract, with no significant difference between isolated and familial cases. The present data seem to reflect the best estimate of the prevalence of genitourinary anomalies in patients with the EEC syndrome. © 1992 Wiley‐Liss, Inc.
Possible relationship between ulnar‐mammary syndrome and split hand with aplasia of the ulna syndrome
Authors: Franceschini P. , Vardeu M. P. , Dalforno L. , Signorile F. , Franceschini D. , Lala R. , Matarazzo P.
Published: June 2005

We describe a 3‐generation family in which mother, maternal grandfather, and 2 (male and female) children have variably manifestations of the ulnar‐mammary syndrome, including ulnar ray defects, obesity, hypogenitalism, delayed puberty, hypoplasia of nipples and apocrine glands, and a previously undescribed ectopia of upper canines. The index patient also had split‐hand appearance on the right due to complete absence of the 4th ray. To our knowledge this is the first documented example of split hand in the ulnar‐mammary syndrome. The hand anomaly raises the question of a possible causal relationship between ulnar‐mammary syndrome and the split hand with aplasia of the ulna syndrome, as already hypothesized by Lenz [1980]. © 1992 Wiley‐Liss, Inc.
Cytogenetic guidelines for fragile X studies tested in routine practice
Authors: Dewald Gordon W. , Buckley Diane D. , Spurbeck Jack L. , Jalal Syed M.
Published: June 2005

Several organizations have proposed guidelines for fra(X) studies on peripheral blood lymphocytes. To evaluate these guidelines, we reviewed 1,033 consecutive specimens referred for fra(X) analysis. Each specimen was cultured with medium 199 and RPMI 1640 with 5‐fluorodeoxyuridine or excess thymidine. The karyotype and expression of fra(X) were established from 20 GTL‐ or QFQ‐banded cells and by screening of up to 130 more banded cells. We found anomalies other than fra(X) in 37 (3.6%) of the patients. We found 4% or more fra(X) cells in 38 (3.7%) cases from 36 unrelated families, including 33 (3.9%) of 850 males and 5 (2.7%) of 183 females. Another 4 females had 1 to 3% fra(X) cells. Six specimens were fra(X)‐positive in only one stress system, and 32 were positive in 2 systems. To find the first 2 fra(X) cells in males, we needed to study up to 36 cells in 31 cases, 50 in one case, and 57 in another. To find the first 2 fra(X) cells in females, we needed to study up to 17 cells in 4 cases and 57 in another. A strong family history of fra(X) occurred in 5 patients, and each one was fra(X)‐positive. Some manifestations of the fragile X syndrome occurred in 507 cases, 17 (3%) of which were fra(X)‐positive. Abnormalities considered unlikely to be the fragile X syndrome occurred in 103 cases, 3 (3%) of which were fra(X)‐positive. Use of chromosome breakage and fra(3)(p14) as quality control indicators of the fra(X) stress systems was found to be unreliable. Our findings support most of the proposed guidelines for fra(X) studies but indicate a need for modifications of others. © 1992 Wiley‐Liss, Inc.
Prenatal exclusion of choroideremia
Authors: van den Hurk J. A. J. M. , van Zandvoort P. M. , Brunsmann F. , Pawlowitzki I. H. , Holzgreve W. , Szabo P. , Cremers F. P. M. , van Oost B. A.
Published: June 2005

We performed prenatal testing to predict the inheritance of choroideremia (CHM) using a linked polymorphic DNA marker, DXS95. DNA analysis of chorionic villi at the 12th week of pregnancy indicated that the allele at risk had not been passed from the heterozygous mother to the fetus. This prenatal exclusion of choroideremia was confirmed by polymerase chain reaction‐single‐strand conformation polymorphism (PCR‐SSCP) analysis. © 1992 Wiley‐Liss, Inc.
Female twin with hunter disease due to nonrandom inactivation of the X‐chromosome: A consequence of twinning
Authors: Winchester Bryan , Young Elisabeth , Geddes Stella , Genet Sally , Hurst Jane , Middelton‐Price Helen , Williams Nicola , Webb Michael , Habel Alex , Malcolm Susan
Published: June 2005

We report the occurrence of Hunter disease (mucopolysaccharidosis type II) in a karyotypically normal girl who was one of identical twins. Molecular studies showed nonrandom X‐inactivation in both her fibroblasts and lymphocytes, while her normal twin showed equal usage of both X chromosomes. In view of previous reports of 7 pairs of identical female twins in which one had Duchenne muscular dystrophy, it seems that twinning may be strongly associated with nonrandom X‐inactivation, and is not specific to the properties of the disease causing gene. © 1992 Wiley‐Liss, Inc.
Osteoporosis‐pseudoglioma syndrome
Authors: de Paepe Anne , Leroy Jules G. , Nuytinck Lieve , Meire Françoise , Capoen Jan
Published: June 2005

Two patients with osteoporosis pseudoglioma syndrome are described. Both are single children, born to nonconsanguineous, healthy parents.

The first patient, a 17‐year‐old girl, had serious visual impairment since birth. She is severely dwarfed and has major skeletal deformities resulting in inability to walk since age 2 years.

The second patient is an 18‐year‐old girl with unilateral neonatal blindness, short stature and deformities, mainly of pelvis and lower limbs. She has been able to walk with support up to now. The clinical and radiological findings in these 2 patients reflect the clinical variability of the condition.

Results of collagen studies in both patients are normal and differentiate this condition clearly from severe osteogenesis imperfecta, which it resembles. © 1993 Wiley‐Liss, Inc.
Potential role of an additive genetic component in the cause of amyotrophic lateral sclerosis and parkinsonism‐dementia in the western Pacific
Authors: Bailey‐Wilson Joan E. , Plato Chris C. , Elston Robert C. , Garruto Ralph M.
Published: June 2005

Amyotrophic lateral sclerosis (ALS) and parkinsonism‐dementia (PD) are neurological degenerative disorders that occur in three high incidence foci in the western Pacific: among the Chamorros of Guam and the Commonwealth of the Northern Marianas Islands, among Japanese on the Kii peninsula of Honshu Island, and among the Auyu and Jakai peoples of southern West New Guinea. Previous studies have implicated both genetic susceptibility and environmental risk factors in the causation and familial clustering of these disorders. The data analyzed consist of 2,026 individuals in nuclear families ascertained on Guam through two mechanisms: (1) nuclear families were included in the study if one or both parents in the family were affected with ALS or PD or both; and (2) a group of “controls” was selected by obtaining nuclear families where neither parent was affected and both had lived through the age of risk. Clinically, ALS and PD are two distinct disorders. However, preliminary analyses indicated that combining all three diagnoses into one affected diagnosis for genetic analyses (thereby assuming any genetic effect on susceptibility to the two disorders was due to the same genetic mechanism) was reasonable. An age, sex and birth cohort‐specific liability was defined and segregation analysis was performed under both logistic and normal models for this liability at the time of disease onset. Under either model, purely environmental, Mendelian dominant and Mendelian recessive hypotheses could be rejected, but a two‐allele additive major locus hypothesis could not be rejected. © 1993 Wiley‐Liss, Inc.
National Neurofibromatosis Foundation International Database
Authors: Friedman J. M. , Birch Patricia , Greene Carol ,   NNFF International Database Participants
Published: June 2005

The National Neurofibromatosis Foundation International Database is a system for collecting comprehensive information on the clinical manifestations and natural history of neurofibromatosis. Data are entered into personal computers at participating centres and are pooled at the Central Database and coordinating centre in Vancouver, Canada. The system includes special mechanisms to assure consistency among centres and to maintain patient confidentiality. The database is designed to foster collaborative clinical and molecular genetic research in many aspects of neurofibromatosis. © 1993 Wiley‐Liss, Inc.