bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurofibromatosis type I (NFI) in Israeli families: Linkage analysis as a diagnostic tool
Authors: Elyakim Segal , Lerer Israela , Zlotogora Joel , Sagi Michal , Gelman‐Kohan Zully , Merin Saul , Abeliovich Dvorah
Published: June 2005

Linkage analysis of 18 neurofibromatosis type I (NFI) families was performed using intragenic and flanking polymorphic markers. The aims of the analysis were prenatal diagnosis of at‐risk fetuses, and of asymptomatic individuals who were relatives of NFI patients. Prenatal diagnosis was performed in 9 pregnancies of 7 families; 5 fetuses were diagnosed as affected. In 6 families with an affected spouse, the request was to identify informative polymorphisms to be used in future pregnancies. Presymptomatic diagnosis was performed in 4 families. One individual, a brother of an NFI patient, was found to have Lisch nodules as the only NFI symptom. Linkage analysis indicated that if this person is a carrier of the NFI gene, he must be a product of intragenic crossover. In 2 individuals with a new NFI mutation, the origin of the NFI‐bearing chromosomes was paternal. The same observation was noted by others. A summary of published cases shows that some 90% of the NFI‐bearing chromosomes of patients with new mutations were of paternal origin. We therefore suggest that for the purpose of prenatal diagnosis in carriers of NFI new (and unidentified) mutations, the paternal chromosome will be considered as the NFI‐bearing chromosome. © 1994 Wiley‐Liss, Inc.
Autosomal dominant (Beukes) premature degenerative osteoarthropathy of the hip joint unlinked to COL2A1
Authors: Beighton Peter , Cilliers Hendrik J. , Ramesar Rajkumar
Published: June 2005

Molecular investigations have been undertaken in several separate large South African families with autosomal dominant skeletal dysplasias in which premature degenerative osteoarthropathy of the hip joint was the major manifestation. There are sometimes additional minor changes in the spine and these conditions fall into the general spondyloepiphyseal dysplasia (SED) nosological category. In some kindreds, linkage between phenotype and the type II collagen gene (COL2A1) has been established, while in others there is no linkage. We have now completed molecular linkage investigations in an Afrikaner family named Beukes, in which 47 members in 6 generations have premature osteoarthropathy of the hip joint. A LOD score of minus infinity indicates that this condition is not the result of a defect of the COL2A1 gene. © 1994 Wiley‐Liss, Inc.
Potential use of buccal smears for rapid diagnosis of autosomal trisomy or chromosomal sex in newborn infants using DNA probes
Authors: Harris Charles , Wilkerson Craig , Clark Karen , Lazarski Kathra , Meisner Lorraine
Published: June 2005

Buccal smears from 3 women and 1 man were probed with alpha satellite DNA probes for chromosomes 8, 18, X, and Y. Buccal smears were also collected from an adolescent phenotypic female with uterine agenesis, as well as from newborn infants with suspected trisomy 18 and trisomy 21. The clinical cases were confirmed with conventional cytogenetic studies of peripheral lymphocytes. Overall probe efficiency at detecting expected chromosome number in interphase cells was found to be 71% ± 6.8%. Higher than expected n‐1 signal numbers may be due to karyopyknotic intermediate epithelial cells present in all collected samples. Overall probe efficiency was found to be consistent using alpha satellite and cosmid probes, both of which accurately reflected the modal copy number of the target chromosomes. False trisomy was less than 1%. This study suggests DNA probes can be used in buccal smears for rapid diagnosis of trisomies and chromosomal sex in new‐borns, but because of high rates of false hypoploid signals, probed buccal smear specimens may not be accurate at diagnosing mosaicism. © 1994 Wiley‐Liss, Inc.
Small terminal deletions of the long arm of chromosome 2: Two new cases
Authors: Fisher Andrew M. , Ellis Katrina H. , Browne Caroline E. , Barber John C. K. , Barker Margaret , Kennedy Colin R. , Foley Helen , Patton Michael A.
Published: June 2005

We report on 2 girls with small de novo terminal deletions of the long arm of chromosome 2 and breakpoints within q37. Four cases with similar or more extensive deletions have been previously reported in full. Hypotonia and psychomotor retardation were the only manifestations common to all 6 cases. The phenotype associated with small terminal 2q deletions is variable and clearly not always as mild as indicated in previous reports. The abnormality may also be more common than has been assumed. © 1994 Wiley‐Liss, Inc.
Relationship between homozygosity at the dopamine D3 receptor gene and schizophrenia
Authors: Mant R. , Williams J. , Asherson P. , Parfitt E. , McGuffin P. , Owen M. J.
Published: June 2005

We have reported an association between schizophrenia and homozygosity of a Bal I polymorphism in the first exon of the dopamine D3 receptor gene (Crocq et al.: Journal of Medical Genetics 29:858–860, 1992). The present study consists of an attempt to replicate this finding in a further sample of 66 patients and 97 controls. Once again more patients than controls were homozygous, but the effect was not as strong as in our first study (χ2 = 2.53, P = 0.05, one tailed). When pooled data from our two studies were analysed, excess homozygosity in patients remained highly significant (P = 0.002) with a particular excess of the 1 : 1 genotype (P = 0.01). This reflected a departure from Hardy‐Weinberg equilibrium in the patients (P = 0.0005) but not the controls (P = 0.24). This led us to explore the possibility that there might be important differences between the patients in our two studies and that excess homozygosity might be a characteristic of particular subgroups of schizophrenics. Our findings suggest that the effect is consistently at its strongest in those patients who have a high familial loading and in those who have a good response to neuroleptic treatment, and that differences between our two samples might have contributed to the quantitatively different outcomes. © 1994 Wiley‐Liss, Inc.
Sequential strategy to identify a susceptibility gene for schizophrenia: Report of potential linkage on chromosome 22q12‐q13.1: Part 1
Authors: Pulver Ann E. , Karayiorgou Maria , Wolyniec Paula S. , Lasseter Virginia K. , Kasch Laura , Nestadt Gerald , Antonarakis Stylianos , Housman David , Kazazian Haig H. , Meyers Deborah , Ott Jurg , Lamacz Malgorzata , Liang Kung‐Yee , Hanfelt John , Ullrich Gail , DeMarchi Nicola , Ramu Elango , McHugh Paul R. , Adler Lawrence , Thomas Marion , Carpenter William T. , Manschreck Theo , Gordon C. T. , Kimberland Michelle , Babb Robert , Puck Jennifer , Childs Barton
Published: June 2005

To identify genes responsible for the susceptibility for schizophrenia, and to test the hypothesis that schizophrenia is etiologically heterogeneous, we have studied 39 multiplex families from a systematic sample of schizophrenic patients. Using a complex autosomal dominant model, which considers only those with a diagnosis of schizophrenia or schizoaffective disorder as affected, a random search of the genome for detection of linkage was undertaken. Pairwise linkage analyses suggest a potential linkage (LRH = 34.7 or maximum lod score = 1.54) for one region (22q12‐q13.1). Reanalyses, varying parameters in the dominant model, maximized the LRH at 660.7 (maximum lod score 2.82). This finding is of sufficient interest to warrant further investigation through collaborative studies. © 1994 Wiley‐Liss, Inc.
Genomic scan for genes predisposing to schizophrenia
Authors: Coon Hilary , Jensen Steven , Holik John , Hoff Mark , Myles‐Worsley Marina , Reimherr Fred , Wender Paul , Waldo Merilyne , Freedman Robert , Leppert Mark , Byerley William
Published: June 2005

We initiated a genome‐wide search for genes predisposing to schizophrenia by ascertaining 9 families, each containing three to five cases of schizophrenia. The 9 pedigrees were initially genotyped with 329 polymorphic DNA loci distributed throughout the genome. Assuming either autosomal dominant or recessive inheritance, 254 DNA loci yielded lod scores less than −2.0 at θ = 0.0, 101 DNA markers gave lod scores less than −2.0 at θ = 0.05, while 5 DNA loci produced maximum lod scores greater than 1: D4S35, D14S17, D15S1, D22S84, and D22S55. Of the DNA markers yielding lod scores greater than 1, D4S35 and D22S55 also were suggestive of linkage when the Affected‐Pedigree‐Member method was used. The families were then genotyped with four highly polymorphic simple sequence repeat markers; possible linkage diminished with DNA markers mapping nearby D4S35, while suggestive evidence of linkage remained with loci in the region of D22S55. Although follow‐up investigation of these chromosomal regions may be warranted, our linkage results should be viewed as preliminary observations, as 35 unaffected persons are not past the age of risk. © 1994 Wiley‐Liss, Inc.
Lack of association between obsessive‐compulsive disorder and the dopamine D3 receptor gene: Some preliminary considerations
Authors: Catalano Marco , Sciuto Gabriella , Di Bella Daniela , Novelli Emanuela , Nobile Maria , Bellodi Laura
Published: June 2005

Controversial results possibly suggesting an association between Tourette's Syndrome (TS) and excess of homozygosity at a Msc I polymorphism in the Dopamine D3 receptor (DRD3) gene have recently been reported. Since a relationship between Obsessive‐Compulsive Disorder (OCD) and Tourette's Syndrome (TS) has been suggested, in this study we assessed the frequency of this 2‐allele polymorphism in a sample of 97 OCD patients and in 97 control subjects. No statistically significant differences in allele or genotype frequencies were found. Thus this mutation in the coding sequence of the DRD3 gene is unlikely to confer susceptibility to OCD. © 1994 Wiley‐Liss, Inc.
Obesity in heterozygous carriers of the gene for the Bardet‐Biedl syndrome
Authors: Croft Janet B. , Morrell Daphne , Chase Charles L. , Swift Michael
Published: June 2005

Obesity and renal failure are common manifestations in the autosomal recessive Bardet‐Biedl (BB) syndrome. Because obesity and hypertension have been reported frequently in non‐homozygous relatives of BB patients, we hypothesized that BB heterozygotes are predisposed to these conditions. Clinical information was collected from 34 parents of BB homozygotes, who are obligate heterozygotes. The proportion of severely overweight fathers (26.7%) was significantly higher than that in comparably aged United States white males (8.9%). We conclude that the BB gene may predispose male heterozygous carriers to obesity. If BB heterozygotes are 1% of the general population, we estimate that approximately 2.9% of all severely overweight white males carry a single BB gene. The BB parents of both sexes were also significantly taller than U.S. white men and women of comparable age. © 1995 Wiley‐Liss, Inc.
Natural history study of hereditary multiple exostoses
Authors: Wicklund C. Luckert , Pauli R. M. , Johnston D. , Hecht J. T.
Published: June 2005

Hereditary multiple exostosis (EXT) is an autosomal dominant disorder in which the clinical hallmark is the growth of bony protuberances from long bones and which can cause a variety of orthopedic deformities. This study sought to further delineate the natural history of EXT. In addition, since previous studies have suggested that there are deviations from Mendelelian expectations in EXT, including incomplete penetrance and a skewed sex ratio, we attempted to confirm or refute these suggestions. Both portions of the study were carried out through retrospective review of 43 affected probands and 137 of their affected relatives. Data are presented concerning frequency and severity of complications of EXT including short stature, sequelae of exostoses, occurrence of malignant degeneration of exostoses, and problems in pregnancy and delivery of affected females. Only 2.8% of the total affected population had experienced exostosis‐related malignancy, an estimate which is considerably less than earlier reports would suggest. Penetrance was 100%. There was an excess of males within the entire affected population (104:76) and within identified probands (28:15). However, the male to female ratio was unskewed in nuclear families (probands, affected sibs, and parents). The excess of males appears to be related to males having more severe and more frequent complications of EXT than having any primary genetic origin. © 1995 Wiley‐Liss, Inc.
XX true hermaphroditism in Southern African Blacks: Exclusion of SRY sequences and uniparental disomy of the X chromosome
Authors: Spurdle Amanda B. , Shankman Sara , Ramsay Michele
Published: June 2005

A molecular investigation of 16 Bantu‐speaking Black XX true hermaphrodites was undertaken in an attempt to determine the cause of the disorder. Y‐specific sequences, including sequences mapping to the sexdetermining region of the Y, were shown to be absent from lymphocyte tissue of all 16 patients tested. Y chromosome sequences were also absent from the ovarian and testicular components of both ovotestes of a single XX true hermaphrodite, thus excluding gonadal mosaicism involving Y chromosome sequences. Since there is evidence for Xp genes involved in testis determination/differentiation, uniparental disomy of the X chromosome was investigated in 14 XXTH families. Uniparental disomy was excluded in 12 of the 14 families, and isodisomy was excluded in the remaining two cases. © 1995 Wiley‐Liss, Inc.
Fifty probands with extra structurally abnormal chromosomes characterized by fluorescence in situ hybridization
Authors: Blennow Elisabeth , Nielsen Karen Brøndum , Telenius Håkan , Carter Nigel P. , Kristoffersson Ulf , Holmberg Eva , Gillberg Christopher , Nordenskjöld Magnus
Published: June 2005

Extra structurally abnormal chromosomes (ESACs) are small supernumerary chromosomes often associated with developmental abnormalities and malformations. We present 50 probands with ESACs characterized by fluorescence in situ hybridization using centromere‐specific probes and chromosome‐specific libraries. ESAC‐specific libraries were constructed by flow sorting and subsequent amplification by DOP‐PCR. Using such ESAC‐specific libraries we were able to outline the chromosome regions involved.

Twenty‐three of the 50 ESACs were inverted duplications of chromosome 15 [inv dup(15)], including patients with normal phenotypes and others with similar clinical symptoms. These 2 groups differed in size and shape of the inv dup(15). Patients with a large inv dup(15), which included the Prader‐Willi region, had a high risk of abnormality, whereas patients with a small inv dup(15), not including the Prader‐Willi region, were normal. ESACs derived from chromosomes 13 or 21 appeared to have a low risk of abnormality, while one out of 3 patients with an ESAC derived from chromosome 14 had discrete symptoms. One out of 3 patients with an ESAC derived from chromosome 22 had severe anomalies, corresponding to some of the manifestations of the cat eye syndrome. Small extra ring chromosomes of autosomal origin and ESACs identified as i(12p) or i(18p) were all associated with a high risk of abnormality. © 1995 Wiley‐Liss, Inc.
A common FGFR3 gene mutation is present in achondroplasia but not in hypochondroplasia
Authors: Stoilov Ivaylo , Kilpatrick Michael W. , Tsipouras Petros
Published: June 2005

Achondroplasia is the most common type of genetic dwarfism. It is characterized by disproportionate short stature and other skeletal anomalies resulting from a defect in the maturation of the chondrocytes in the growth plate of the cartilage. Recent studies mapped the achondroplasia gene on chromosome region 4p 16.3 and identified a common mutation in the gene encoding the fibroblast growth factor receptor 3 (FGFR3). In an analysis of 19 achondroplasia families from a variety of ethnic backgrounds we confirmed the presence of the G380R mutation in 21 of 23 achondroplasia chromosomes studied. In contrast, the G380R mutation was not found in any of the 8 hypochondroplasia chromosomes studied. Furthermore, linkage studies in a 3‐generation family with hypochondroplasia show discordant segregation with markers in the 4p 16.3 region suggesting that at least some cases of hypochondroplasia are caused by mutations in a gene other than FGFR3. © 1995 Wiley‐Liss, Inc.
New heritable fragile site with spontaneous expression at 1q41
Authors: Dar Hanna , Bar‐El Hanna , Ziv Mira , Shapiro Israel
Published: June 2005

The report presents a family ascertained through recurrent spontaneous abortions in which a new heritable fragile site located at 1q41 is segregating. The fragile site is present in the mother and her son. It is expressed spontaneously in 100% of the metaphases from lymphocyte culture using standard conditions. The use of folate deficient medium and the addition of FUdR to the medium did not affect the appearance nor the level of expression of the fragile site. © 1995 Wiley‐Liss, Inc.
Prenatal diagnosis of recurrence of short rib‐polydactyly syndrome
Authors: Wu Meng‐Hsing , Kuo Pao‐Lin , Lin Shio‐Jean
Published: June 2005

We describe a nonconsanguineous couple whose 3 successive pregnancies, including one pair of twins, led to the birth of 4 infants with short rib‐polydactyly syndrome (SRPS). Flat face, hypoplastic thorax, short limbs and ribs, polydactyly, absence of penis, and death after birth were noted in the first affected male baby. The affected female twins were detected prenatally by ultrasonography and had the same characteristics, but milder than the previous one. Serial measurements of the thoracic circumference and the 4 limbs were obtained by ultrasound, and showed progressively decreased ratio of thoracic to abdominal circumference and shortness of the limbs. The last male baby also had a similar but variable expression in prenatal ultrasonography. © 1995 Wiley‐Liss, Inc.
Clinical and hematologic aspects of the X‐linked α‐thalassemia/mental retardation syndrome (ATR‐X)
Authors: Gibbons R. J. , Brueton L. , Buckle V. J. , Burn J. , Clayton‐Smith J. , Davison B. C. C. , Gardner R. J. M. , Homfray T. , Kearney L. , Kingston H. M. , Newbury‐Ecob R. , Porteous M. E. P. , Wilkie A. O. M. , Higgs D. R.
Published: June 2005

The hallmarks of the X‐linked α‐thalassemia/mental retardation (ATR‐X) syndrome are severe psychomotor retardation, minor facial anomalies, genital abnormalities, and an unusual form of α‐thalassemia. The demonstration of HbH inclusions in red blood cells after incubation with brilliant cresyl blue confirms the diagnosis. We describe 15 previously unreported cases and analyse the phenotypic and hematologic findings in these subjects and compare them with previously published cases. This study demonstrates the consistency of the main characteristics of this syndrome and extends the phenotype. Developmental changes in phenotype, in particular the coarsening of the facial appearance, are illustrated. The hematologic findings are shown to vary widely; in some cases the manifestation of α‐thalassemia may be subtle and missed without repeated examination. © 1995 Wiley‐Liss, Inc.
Lethal congenital non‐spherocytic, non‐immune hemolytic anemia with genital and other anomalies in two brothers
Authors: Waters Brenda L. , West Barbara R.
Published: June 2005

Non‐consanguineous healthy parents had 2 boys with severe, non‐spherocytic, nonimmune hemolytic anemia, abnormalities of their external genitalia, flat occiput, dimpled earlobes, deep plantar creases, and increased space between their first and second toes. The birth of these children was separated by a spontaneous abortion at 3 months and delivery of a normal girl. We propose that these boys have a heretofore undescribed autosomal or X‐linked recessive syndrome. © 1995 Wiley‐Liss, Inc.
Clitoromegaly in neurofibromatosis
Authors: Sutphen Rebecca , Galán‐Goméz Enrique , Kousseff Boris G.
Published: June 2005

Genitourinary neurofibromas are rare and clitoral involvement in neurofibromatosis (NF) has been reported infrequently. However, when it occurs, clitoromegaly is often the presenting sign. In many cases, it is congenital. In 236 families with type 1 neurofibromatosis (NF‐1) evaluated through the USF Regional Genetics Program between January 1982 and September 1993, four patients had clitoral involvement. In three, involvement was limited to the clitoris. Biopsy/surgical excision in two of them showed a neurofibroma in one and non‐specific hamartomatous soft tissue overgrowth in the other. In the fourth patient, the involvement was asymmetric and extended to the labia majora and mons pubis. Endocrine studies and chromosomes in all patients were normal; there was no exposure to androgens, progestins, or coumadin. There was no gestational history of maternal luteomas. Review of the literature documented 26 patients with NF and clitoral involvement.

Clitoral involvement in NF‐1 appears to be more common than previously reported and the differential diagnosis of ambiguous genitalia should include clitoromegaly due to NF. Pathogenesis of clitoral lesions appears similar to other lesions of NF. Biopsy of such lesions appears to be justified only when malignancy is suspected. © 1995 Wiley‐Liss, Inc.
Genetic, environmental, and phenotypic links between body mass index and blood pressure among women
Authors: Allison David B. , Heshka Stanley , Neale Michael C. , Tishler Peter V. , Heymsfield Steven B.
Published: June 2005

Greater relative weight is associated with higher blood pressure, but the reasons are unknown. The inability of current technology to inducesustainedweight loss among overweight persons precludes experimental tests of whether this association is causal. We evaluated the degree to which thecovariationbetween body mass index (BMI; kg/m2) and blood pressure (BP) among women is due to pleiotropic genetic factors, environmental factors, or phenotypic causation. The sample included 75 monozygotic (MZ) and 39 dizygotic (DZ) pairs of adult female twins. “BP” was calculated as the unitweighted mean of systolic and diastolic. Data were analyzed through structural equation modeling. A model was specified stipulating that additive genetic effects (A) and unique environmental effects (E) each contributed to the covariance between BMI and BP, thus allowing for both pleiotropic and unique environmental influences on the covariance between BMI and BP. Dropping the pleiotropic influences significantly worsened the model (χ2= 4.62, df = 1,P= .032), suggesting significant pleiotropic effects. Dropping the environmental influences on the cross‐phenotype covariance did not significantly worsen the model (χ2= 1.42, df = 1,P=.233). This indicates no significant effect of the environment on the covariance between BMI and BP. Finally, a model of phenotypic causation in which BMI directly influenced BP was fitted. This model provided the best single parameter explanation of the BP‐BMI covariation. These data suggest that, among women, regardless of the source of variation, chaanges in BMI should lead to long‐standing changes in BP. © 1995 Wiley‐Liss, Inc.
Mulibrey nanism: Three additional patients and a review of 39 patients
Authors: Lapunzina Pablo , Rodríguez José Ignacio , de Matteo Elena , Gracia Ricardo , Moreno Felipe
Published: June 2005

We report on 3 patients with Mulibrey nanism (MN), or Perheentupa syndrome: the first 2 sibs from Argentina and a new patient from Spain. All 3 patients had growth failure, short stature, abnormal pigmentary retinal changes, and a J‐shaped sella turcica. These findings are considered major criteria of MN. Two had pericardial constriction, which is a frequent and lifethreatening abnormality in this syndrome.

MN is a rare autosomal recessive condition. Reviewing the 39 patients described so far, we have classified the anomalies into the very frequent (present in more than 66%), frequent (in at least 25%), and not frequent. Identifying the anomalies specific to MN should help its early diagnosis and treatment. © 1995 Wiley‐Liss, Inc.
Myopathy, lactic acidosis, and sideroblastic anemia: A new syndrome
Authors: Inbal Aida , Avissar Nelly , Shaklai Mati , Kuritzky Arieh , Schejter Abel , Ben‐David Eitan , Shanske Sara , Garty Ben‐Zion
Published: June 2005

We describe 2 sibs (brother and sister) with myopathy, sideroblastic anemia, lactic acidosis, mental retardation, microcephaly, high palate, high philtrum, distichiasis, and micrognathia. Very low levels of cytochromes a, b, and c were detected in the patients' muscle mitochondria. Deposition of iron within the mitochondria of bone marrow erythroblasts was observed on electron microscopy. Irregular and enlarged mitochondria with paracrystalline inclusions were also seen on electron microscopy of the patients' muscle specimen. Examination of DNA from the affected sibs showed no deletions in the mitochondrial DNA nor the mutations identified in the syndromes of mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS) or myoclonus, and epilepsy associated with rugged‐red fibers (MERRF).

Since the parents were first cousins and 2 of 6 sibs (male and female) were affected, we suggest that the syndrome expressed by our patients represents a previously unknown autosomal recessive disorder that includes mitochondrial myopathy, lactic acidosis, and sideroblastic anemia. © 1995 Wiley‐Liss, Inc.
Girl with signs of Pelizaeus‐Merzbacher disease heterozygous for a mutation in exon 2 of the proteolipid protein gene
Authors: Hodes M. E. , Demyer William E. , Pratt Victoria M. , Edwards Mary K. , Dlouhy Stephen R.
Published: June 2005

We studied a female infant with clinical signs of Pelizaeus‐Merzbacher disease (PMD), who has a familial mutation (C41 →T) in exon 2 of the proteolipid protein gene (PLP), and selected relatives. While the carrier mother and grandmother of the proposita currently are neurologically normal and show normal T2 magnetic resonance imaging (MRI) of the brain, the infant has a neurological picture, MRIs, and brain auditory evoked response (BAER) consistent with that diagnosis. The data here presented show that PMD can occur in females carrying a mutation in the PLP gene. Our experience with the MRIs of this patient, her mother and grandmother, and those of a previously reported family [Pratt et al.: Am J Med Genet 38:136–139, 1991] show that molecular genetic analysis and not MRI is the appropriate means for carrier detection. © 1995 Wiley‐Liss, Inc.
Dominant distal arthrogryposis in a Maori family with marked variability of expression
Authors: Klemp Patrick , Hall Judith G.
Published: June 2005

The index case was a Maori bushman who presented with severe congenital spinal stenosis and manifestations of distal arthrogryposis. His offspring and 8 of his 9 sibs and most of their offspring were interviewed and examined. Of those examined 7 individuals with definite and 2 with probable distal arthrogryposis were identified in 4 of the families. A tenth relative with distal arthrogryposis and contractural arachnodactyly had died. There was marked variability in the severity and nature of manifestations with 2 having severe hand and foot involvement in addition to craniofacial changes compatible with a diagnosis of Freeman‐Sheldon syndrome. Other apparently unrelated hereditary disorders in the family included ectrodactyly, biliary atresia, and Brachmann‐de Lange syndrome. This is the first report of arthrogryposis in a Maori family. © 1995 Wiley‐Liss, Inc.
Balanced nonacrocentric whole‐arm reciprocal translocations: A de novo case and literature review
Authors: Farrell S. A. , Fan Yao‐Shan
Published: June 2005

We report a new de novo case of a balanced whole‐arm reciprocal translocation, detected at prenatal diagnosis for late maternal age. A review of previous cases indicates there is a risk of chromosomally abnormal liveborn offspring when a parent is a carrier of this type of translocation, particularly when the translocated region is a small chromosomal segment. Due to the limited number of cases, exact reproductive risks are not available. This is the second example of such a translocation of chromosomes 1 and 5, raising the possibility of nonrandom involvement of certain chromosomes in balanced nonacrocentric whole‐arm reciprocal translocations. © 1995 Wiley‐Liss, Inc.
Proximal femoral focal deficiency (PFFD) and fibular a/hypoplasia (FA/H): A model of a developmental field defect
Authors: Sorge Giovanni , Ardito Salvatore , Genuardi Maurizio , Pavone Vito , Rizzo Renata , Conti Giovanni , Neri Giovanni , Katz Ben E. , Opitz John M.
Published: June 2005

Proximal femoral focal deficiency (PFFD) and fibular a/hypoplasia (FAH) are distinct malformations of the lower limbs. Both can occur as isolated defects or in association with other limb malformations. In fact, fibular defects frequently are present in PFFD, and, conversely, femoral abnormalities can be found in the presence of a typical FAH picture. We report on 5 patients with a variable combination of femoral and fibular defects. In one of them unilateral PFFD was associated with lateral foot defects, in the absence of fibular abnormalities, and with a phenotype similar to that observed in the femoral hypoplasia/unusual face syndrome (FH/UFS). Another patient had isolated PFFD on one side, with controlateral absence of femur, fibula, and tibia. Another patient had a PFFD, fibular hypoplasia, and abnormalities of fibular foot rays, and the last 2 patients, a father and son, had, respectively, bilateral foot malformations plus fibular and tibial hypoplasia in the father and a PFFD in the son. These observations represent a further demonstration of the existence of a fibular developmental field, and contribute to the definition of its spatial boundaries. The variable involvement of elements comprised in the developmental field can be explained by multifactorial etiology. © 1995 Wiley‐Liss, Inc.
Detection of Y chromosome sequences in a 45,X/46,XXq– patient by Southern blot analysis of PCR‐amplified DNA and fluorescent in situ hybridization (FISH)
Authors: Kocova Mirjana , Siegel Selma Feldman , Wenger Sharon L. , Lee Peter A. , Nalesnik Michael , Trucco Massimo
Published: June 2005

In some cases of gonadal dysgenesis, cytogenetic analysis seems to be discordant with the phenotype of the patients. We have applied techniques such as Southern blot analysis and fluorescent in situ hybridization (FISH) to resolve the phenotype/genotype discrepancy in a patient with ambiguous genitalia in whom the peripheral blood karyotype was 45,X. Gonadectomy at age 7 months showed the gonadal tissue to be prepubertal testis on the left side and a streak gonad on the right. The karyotype obtained from the left gonad was 45,X/46,XXq‐ and that from the right gonad was 45,X. Three different techniques, PCR amplification, FISH, and chromosome painting for X and Y chromosomes, confirmed the presence of Y chromosome sequences. Five different tissues were evaluated. The highest percentage of Y chromosome positive cells were detected in the left gonad, followed by the peripheral blood lymphocytes, skin fibroblasts, and buccal mucosa. No Y chromosomal material could be identified in the right gonad. Since the Xq‐ chromosome is present in the left gonad (testis), it is likely that the Xq‐ contains Y chromosomal material. Sophisticated analysis in this patient showed that she has at least 2 cell lines, one of which contains Y chromosomal material. © 1995 Wiley‐Liss, Inc.
Genetic study of nonsyndromic coronal craniosynostosis
Authors: Lajeunie Elizabeth , Merrer Martine Le , Bonaïti‐Pellie Catherine , Marchac Daniel , Renier Dominique
Published: June 2005

From a series of 1265 individuals with different craniosynostoses hospitalized between 1976 and 1993, 260 probands with nonsyndromic unilateral (181) or bilateral (79) coronal synostosis were analysed. The prevalence of craniosynostoses was estimated as 1 in 2100 children. In the group of coronal synostosis, family history was obtained on 192 probands in 180 pedigrees. The male:female ratio was 1:2. The average paternal age was 32.7 ± 6.4 years, which is significantly higher than normal. In 26 of the 180 pedigrees, a high degree of familial aggregation was observed, giving a 14.4% figure of familial cases. The bicoronal synostoses were significantly more often familial than the unicoronal synostoses. Segregation analysis of these families leads to the conclusion that coronal synostosis is transmitted as a dominant disorder with 0.60 penetrance and 61% of sporadic cases. © 1995 Wiley‐Liss, Inc.
Asplenia in two father‐son Pairs
Authors: Lindor Noralane M. , Smithson William A. , Ahumada Carlos A. , Michels Virginia V. , Opitz John M.
Published: June 2005

We report on two father‐son pairs with isolated nonsyndromal asplenia. This may represent autosomal dominant inheritance of a mutation in a gene involved with spleen development and determination of laterality. The incidence of hereditary isolated asplenia is unknown; therefore, screening for asplenia in first degree relatives of individuals with (poly)asplenia should be considered. © 1995 Wiley‐Liss, Inc.
Kabuki make‐up (Niikawa‐Kuroki) syndrome in the Byelorussian register of congenital malformations: Ten new observations
Authors: Ilyina Helena , Lurie Iosif , Naumtchik Irena , Amoashy Dmitry , Stephanenko Galina , Fedotov Valery , Kostjuk Albina
Published: June 2005

We describe clinical manifestations and historical data on ten patients with Kabuki make‐up syndrome. All patients are of European ancestry and all have the characteristics of the syndrome, including typical face, retarded physical development, and mild to moderate mental retardation. Two of the probands have low‐normal intelligence. Prominent and broad philtrum was described as an important component manifestation of the syndrome. In three families some clinical manifestations of Kabuki make‐up syndrome were observed in parents and some other relatives of the probands in three generations. Some phenotypic differences between Asian and non‐Asian patients were noted. The possible cause of the syndrome is discussed. The present observations and a literature review suggest autosomal dominant inheritance with different expressivity of the Kabuki make‐up syndrome. © 1995 Wiley‐Liss, Inc.
Family with partial monosomy 10p and trisomy 10p
Authors: Hon Ellis , Chapman Cyril , Gunn Tania R.
Published: June 2005

We report on a family with an abnormality of 10p. The propositus has monosomy for the distal region of 10p and severe psychomotor delay, growth failure, congenital heart defect, multicystic kidney, grade V vesicoureteric reflux, and neurosensory hearing loss. The mother and the elder brother of the propositus carry a balanced reciprocal translocation (5q;10p)(q35.3;p12.3). A retarded and epileptic maternal aunt was found to have dup(10p).

Study of the family history led to the successful obstetric management of a subsequent twin pregnancy in which an affected fetus with dup(10p) was identified and selectively terminated, while the other normal twin was delivered at term without problems. © 1995 Wiley‐Liss, Inc.
Marker chromosome 21 identified by microdissection and FISH
Authors: Sun Yongming , Rubinstein Jack , Soukup Shirley , Palmer Catherine G.
Published: June 2005

A child without Down syndrome but with developmental delay, short stature, and autistic behavior was found to be mosaic 46,XX/47,XX,+mar(21) de novo. The marker was a small ring or dot‐like chromosome. Microdissection of the marker was performed. The dissected fragments were biotinylated with sequence‐independent PCR as a probe pool for fluorescence in situ hybridization (FISH). FISH results suggested an acrocentric origin of the marker. Subsequent FISH with α‐satellite DNA probes for acrocentric chromosomes, and chromosome‐specific 21 and 22 painting probes confirmed its origin from chromosome 21. © 1995 Wiley‐Liss, Inc.
Acrofacial dysostosis of unknown type: Nosology of the acrofacial dysostoses
Authors: Preis Sabine , Raymaekers‐Buntinx Inge , Majewski Frank
Published: June 2005

We describe a stillborn girl with an unclassified form of mandibulofacial dysostosis, a postaxial defect of the right, and a preaxial defect of the left hand. The Nager syndrome is characterized by preaxial limb defects, whereas the Genée‐Wiedemann syndrome (=Miller syndrome) by postaxial limb defects. We briefly review the established acrofacial dysostoses (AFD) and discuss the position of our case in the current classification. © 1995 Wiley‐Liss, Inc.
Severe Smith‐Lemli‐Opitz syndrome with prolonged survival and lipid abnormalities
Authors: Pierquin G. , Peeters P. , Roels F. , Vamos E. , Brucher J. M. , Tint G. S. , Honda A. , Van Regemorter N.
Published: June 2005

We have studied a girl with multiple congenital anomalies, growth and mental deficiency, characteristic facial anomalies, cataracts, cerebellar atrophy, and severe hypocholesterolemia. Death occurred at age 7 years. After excluding several syndromes, i.e., peroxisomal disorders, mevalonic acidaemia, and Marinesco‐Sjögren syndrome, it is concluded that this girl had severe Smith‐Lemli‐Opitz Syndrome (SLOS) with exceptionally long survival. This diagnosis was confirmed through assay of 7‐dehydrocholesterol in cultured fibroblasts. © Wiley‐Liss, Inc.
Inconsistencies in pedigree symbols in human genetics publications: A need for standardization
Authors: Steinhaus Kathryn A. , Bennett Robin L. , Resta Robert G. , Uhrich Stefanie B. , Doyle Debra L. , Markel Dorene S. , Vincent Victoria A.
Published: June 2005

To determine consistency in usage of pedigree symbols by genetics professionals, we reviewed pedigrees printed in 10 human genetic and medical journals and 24 medical genetics textbooks. We found no consistent symbolization for common situations such as pregnancy, spontaneous abortion, death, or test results. Inconsistency in pedigree design can create difficulties in the interpretation of family studies and detract from the pedigree's basic strength of simple and accurate communication of medical information. We recommend the development of standard pedigree symbols, and their incorporation into genetic publications, professional genetics training programs, pedigree software programs, and genetic board examinations. © Wiley‐Liss, Inc.
Clinical and molecular studies in full trisomy 22: Further delineation of the phenotype and review of the literature
Authors: Bacino Carlos A. , Schreck Rhona , Fischel‐Ghodsian Nathan , Pepkowitz Samuel , Prezant Toni R. , Graham John M.
Published: June 2005

Trisomy 22 is commonly found among spontaneous abortions, second in frequency of occurrence only to trisomy 16. Most earlier reports of surviving trisomy 22 cases in the literature are thought to represent the product of unbalanced 11;22 translocations or the result of undetected mosaicism, since this condition is thought to manifest early embryonic or fetal lethality. We present two strikingly similar cases of non‐mosaic trisomy 22 surviving to late gestation. In this paper we emphasize the unique phenotype of this trisomy which included intrauterine growth retardation, microcephaly, broad flat nasal bridge with epicanthal folds and ocular hypertelorism, microtia, variable cleft palate, webbed neck, congenital heart defects involving anomalous great vessels, anorectal and renal anomalies, and hypoplastic distal digits with thumb anomalies. We also explore why some cases survive to late gestation. Confined placental mosaicism, a frequent finding in other lethal trisomies, has been ruled out in one of the cases. Molecular studies done to assess the parental origin of the extra chromosome in the other case showed that the non‐disjunction originated during maternal meiosis II. Parental origin of the extra chromosome does not seem to play a role in late survival for trisomy 22. © 1995 Wiley‐Liss, Inc.
Rieger syndrome with de novo reciprocal translocation t(1;4) (q23.1;q25)
Authors: Makita Yoshio , Masuno Mitsuo , Imaizumi Kiyoshi , Yamashita Sumimasa , Ohba Shizuko , Ito Daizou , Kuroki Yoshikazu
Published: June 2005

We report on a boy with Rieger syndrome, who had an apparently balanced reciprocal translocation between chromosomes 1 and 4. The clinical manifestations of this patient were characterized by irregular shaped pupils with a prominent Schwalbe line and an umbilical hernia. On cytogenetic studies, he was found to have a de novo reciprocal translocation 46,XY,t(1;4) (q23.1;q25), without visible deletion. His parents had normal chromosomes. A review of both cytogenetic and genetic linkage analyses with Rieger syndrome showed that chromosome 4q was involved. This and other previous reports suggested that the gene for Rieger syndrome is mapped to the 4q25→4q26 segment adjoining the breakpoint. © 1995 Wiley‐Liss, Inc.
Absent pituitary gland in two brothers with an oral‐facial‐digital syndrome resembling OFDS II and VI: A new type of OFDS?
Authors: Shashi Vandana , Clark Pamela , Rogol Alan D. , Wilson William G.
Published: June 2005

The oral‐facial‐digital syndromes (OFDS) comprise a group of heterogeneous genetic disorders. Considerable clinical overlap exists within the nine described types [Toriello, Clin Dysmorph 2:95‐105, 1993], and with other entities such as Pallister‐Hall (PH) syndrome and hydrolethalus syndrome, leading to difficulties in the classification of OFDS. We report on two brothers with findings overlapping OFDS II, VI, and Pallister‐Hall syndrome who had congenital absence of the pituitary gland. This may represent a new type of OFDS or, alternatively, an example of phenotypic variability within the OFDS. It also emphasizes that agenesis of the pituitary gland can occur in a variety of syndromes with midline defects. © 1995 Wiley‐Liss, Inc.
Exploration of the effects of predictive testing for Huntington disease on intimate relationships
Authors: Quaid Kimberly A. , Wesson Melissa K.
Published: June 2005

The focus in predictive testing for Hunting‐ton disease is beginning to shift from individuals at risk to an examination of the effects on other relatives, particularly on spouses and partners. We examine the effects of participating in a predictive testing program for 25 couples. When assessed prior to testing, spouses were significantly more depressed than their at‐risk partners. After pretest counseling, 6 (24%) of the couples chose not to pursue testing. At baseline, these 6 couples had significantly higher levels of psychological distress and marital dysfunction than couples who did choose to complete testing.

Of the 19 couples completing testing, 5 received an increased risk result and 14 received a decreased risk result. Prior to testing, the partners of individuals who later received an increased risk result exhibited higher levels of marital distress. At 3‐ and 6‐month follow‐ups, high‐risk couples were significantly more distressed than low‐risk couples. These levels of distress improved somewhat at 9 months after testing, but began to climb again at 12 months.

Individuals at increased risk were significantly more distressed at all points during follow‐up as compared to individuals at low risk. No significant differences were found between the partners of high‐ and low‐risk individuals at 3, 6, 9, and 12 months after disclosure. The significance of these findings and the need to include partners in pretest counseling prior to genetic testing are discussed. © 1995 Wiley‐Liss, Inc.
Parental origin of de novo chromosome 9 deletions in del(9p) syndrome
Authors: Micale Mark A. , Haren J. Marie , Conroy Jeffrey M. , Crowe Carol A. , Schwartz Stuart
Published: June 2005

Parental origin of de novo deletions in the short arm of chromosome 9 in patients with a clinical diagnosis of del(9p) syndrome was assessed in 13 patients using polymerase chain reaction (PCR) analysis of highly polymorphic dinucleotide repeat micro‐satellite markers located in the putative deleted region. The deletion was found to be of paternal origin in 9 cases and of maternal origin in the remaining 4 cases, suggesting that the molecular event resulting in the deletion occurs in both male and female gametogenesis and that genomic imprinting does not appear to play a role in the patho‐genesis of del(9p) syndrome. © 1995 Wiley‐Liss, Inc.
Hands and feet in the Apert syndrome
Authors: Cohen M. Michael , Kreiborg Sven
Published: June 2005

We studied 44 pairs of hands and 37 pairs of feet in Apert syndrome, utilizing clinical, dermatoglyphic, and radiographic methods. We also studied histologic sections of the hand from a 31‐week stillborn fetus. Topic headings discussed include: clinical classification of syndactyly; correlations between types of hands and feet in the same patient; dermatoglyphics; anatomy of the hand; radiologic assessment; comparison with other studies; histologic assessment of the hand; acrocephalosyndactyly vs. acrocephalopoly‐syndactyly: a pseudodistinction; and some generalizations. © 1995 Wiley‐Liss, Inc.
Diaphragmatic hernia in Denys‐Drash syndrome
Authors: Devriendt Koenraad , Deloof Els , Moerman Philippe , Legius Eric , Vanhole Chris , De Zegher Francis , Proesmans Willem , Devlieger Hugo
Published: June 2005

We report on a newborn infant with male pseudohermaphroditism and glomerular lesions (Denys‐Drash syndrome) but without Wilms tumor. A constitutional heterozygous mutation in the WT1 gene (366Arg to His) was identified. In addition the child had a large diaphragmatic hernia, so far not described in Denys‐Drash syndrome. The expression of the WT1 gene in pleural and abdominal mesothelium and the occurrence of diaphragmatic hernia in transgenic mice with a homozygous WT1 deletion strongly suggests that the diaphragmatic hernia in this patient is part of the malformation pattern caused by WT1 mutations. © 1995 Wiley‐Liss, Inc.
Spectrum of X‐linked hydrocephalus (HSAS), MASA syndrome, and complicated spastic paraplegia (SPG1): Clinical review with six additional families
Authors: Schrander‐Stumpel Constance , Höweler Chris , Jones Marilyn , Sommer Annemarie , Stevens Cathy , Tinschert Sigrid , Israel Jeanette , Fryns Jean Pierre
Published: June 2005

X‐linked hydrocephalus (HSAS) (MIM *307000), MASA syndrome (MIM *303350), and complicated spastic paraplegia (SPG1) (MIM *312900) are closely related. Soon after delineation, SPG1 was incorporated into the spectrum of MASA syndrome. HSAS and MASA syndrome show great clinical overlap; DNA linkage analysis places the loci at Xq28. In an increasing number of families with MASA syndrome or HSAS, mutations in L1CAM, a gene located at Xq28, have been reported. In order to further delineate the clinical spectrum, we studied 6 families with male patients presenting with MASA syndrome, HSAS, or a mixed phenotype. We summarized data from previous reports and compared them with our data. Clinical variability appears to be great, even within families. Problems in genetic counseling and prenatal diagnosis, the possible overlap with X‐linked corpus callosum agenesis and FG syndrome, and the different forms of X‐linked complicated spastic paraplegia are discussed. Since adducted thumbs and spastic paraplegia are found in 90% of the patients, the condition may be present in males with nonspecific mental retardation. We propose to abandon the designation MASA syndrome and use the term HSAS/MASA spectrum, incorporating SPG1. © 1995 Wiley‐Liss, Inc.
Neuronal ceroid‐lipofuscinoses in Italy: An epidemiological study
Authors: Cardona Francesco , Rosati Elisabetta
Published: June 2005

To establish the incidence of neuronal ceroid‐lipofuscinoses (NCL) in Italy, we sent a questionnaire to all Neuropediatric and Child Neuropsychiatric Departments (answer rate 15/34 = 44%). Diagnoses were accepted only when based on firm clinical and/or electron microscopic criteria. We collected 58 cases born between 1966–1991 (2 infantile NCL, 37 late infantile NCL, and 19 juvenile NCL). The incidence was calculated only on patients born between 1974–1984.

In this period, the incidence of overall NCL in the Italian population was calculated to be 0.56 per 100,000 live births (0.36 for late infantile NCL, and 0.20 for juvenile NCL).

Our data show that infantile NCL is very rare in Italy, and that late infantile seems to be the most frequent form of NCL. © 1995 Wiley‐Liss, Inc.