bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linkage and genetic counselling for the fragile X using DNA probes 52A, F9, DX13, and ST14
Authors: Mulley John C. , Gedeon Agi K. , Thorn Kerry A. , Bates Lyndall J. , Sutherland Grant R. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractLinkage data using the markers DXS51, F9, DXS15, and DXS52 are presented from 14 pedigrees segregating with the fragile X. Cytogenetic and DNA data were combined by two‐ or three‐point linkage analysis for estimation of lod scores and carrier probabilities in potential carriers. Recombination frequencies (\documentclass{article}\pagestyle{empty}\begin{document}$ \hat \theta $\end{document}) corresponding to maximum z scores (ẑ) were obtained for DXS51 (ẑ = 3.45, \documentclass{article}\pagestyle{empty}\begin{document}$ \hat \theta $\end{document} = 0.0), DXS15 (ẑ = 0.40, \documentclass{article}\pagestyle{empty}\begin{document}$ \hat \theta $\end{document} = 0.06), F9 (ẑ = 3.15, \documentclass{article}\pagestyle{empty}\begin{document}$\hat \theta $\end{document} = 0.09), and DX552 (ẑ = 3.60, \documentclass{article}\pagestyle{empty}\begin{document}$\hat \theta $\end{document} = 0.11) with the fragile X. Considerable alterations to carrier probabilities occurred in some cases, especially when flanking markers were informative. The chance of mentally impaired offspring was reduced to 1% for five of eight women with prior carrier probabilities of 32%. Three pedigrees were identified in which mutation had possibly occurred. An alternative explanation for two of these was inheritance of the fragile X from normal males and for the other inheritance from a clinically normal woman. Probabilities were computed for each of these alternatives.
Gonadal function in patients with Down syndrome
Authors: Hsiang Ying‐Hui H. , Berkovitz Gary D. , Bland Gail L. , Migeon Claude J. , Warren Andrew C. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractGonadal function was evaluated in 100 home‐reared persons with Down syndrome (DS) including 53 boys and men and 47 girls and women. In order to definitively evaluate gondal function in our subjects, all patients with abnormal thyroid function were excluded from endocrine analysis.Among the men, the frequency of hypospadias and cryptorchidism was similar to that of the general population. In both men and women, the ages for the onset and completion of puberty were also normal. However, among adult men with DS, the mean stretched penile length and the mean testicular volume were singnificantly below the mean value of normal men.In the 23 men with DS, the mean serum levels of follicle‐stimulating hormone (FSH) and luteinizing hormone (LH) were significantly eleveted above the mean for normal men. By contrast, the mean plasma level of testosterone (T) was normal, suggesting a diagnosis of partial gonadal deficiency. Among the 14 women in the study, 6 had primary gonadal dysfunction. In prepubertal children, serum FSH levels in 3 boys and 5 girls were more than 2 SD above the mean for normal children, while serum levels of LH in 3 boys and 2 girls were abnormally elevated. When gonadal function was evaluated in male infantss, serum levels of FSH were above the normal in 6 of 11 subjects. Serum LH was abnormally elevated in 3 of 8 female infants.Our data argue that primary gonadal deficiency is common in DS, that it is progressive from birht to adolescence, and that it is clearly manifest in adult patients.
Congenital anomalies: Mortality and morbidity, burden and classification
Authors: Chung Chin S. , Myrianthopoulos Ntinos C. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThis study has attempted to assess the burden imposed by congenital anomalies in terms of postnatal mortality and morbidity, which were in turn used to classify anomalies as severe and mild types. Factors studied were postnatal mortality through age 7 years and morbidity, as measured by neurologic and psychologic abnormalities, histories of major surgery, prolonged hospitalization, and chronic infections. The study was based on a prospective study of 52,332 liveborn singletons of the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke. In general, the highest degree of burden was observed in syndromes and sequences, followed by multiple and single major anomalies. The burden due to major abnormalities as measured by attributable risk ranged from 0.436 for prolonged hospitalization up to one year, to 0.010 for chronic infections in subjects 1–7 years of age. In terms of mortality, the total attributable risk was 0.164, and the mean potential years of life lost was 5,020 per 10,000 population, which is considerably greater than that reported in other studies. An index constructed from mortality, neurologic, psychologic, and surgical variables provides a reasonable and objective means for classifying anomalies into severe and mild types.
The relationship between fetal hemoglobin and disease severity in children with sickle cell anemia
Authors: Odenheimer Daniel J. , Sarnaik Sharada A. , Whitten Charles F. , Rucknagel Donald L. , Sing Charles F. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractA study was conducted in a sample of 140 children with sickle cell anemia to evaluate the relationship between hematological variables (%HbF, %HbA2, %Hb, and mean cell volume) and disease severity. A patient's severity status was determined by whether he/she was hospitalized, had a transfusion, and/or had a pain crisis at 2 evaluation periods; the first was based on a patient's history taken at the initial assessment visit to the Wayne State Comprehensive Sickle Cell Center, and the second was based on a 1–3 year follow‐up at the center. Fetal hemoglobin was a strong predictor of a patient's hospitalization and transfusion status. A decrease in %HbF of 4.76% (one SD of %HbF) was associated with a 3.58 fold (95% confidence interval, 1.18–7.28) greater odds of being hospitalized both prior to initial assessment and on follow‐up, compared to not being hospitalized at either evaluation. Similarly, a decrease in %HbF of 4.76% was associated with a 5.56 fold (95% confidence interval, 1.67–18.96) greater odds of having a transfusion both prior to initial assessment and on follow‐up compared to not having a transfusion at either evaluation. Patients who were both hospitalized and transfused at initial assessment and on follow‐up (n = 12) had a mean %HbF of 7.59%, while patients who were not hospitalized or transfused at either evaluation (n = 19) had a mean %HbF of 13.61%. Fetal hemoglobin was not a significant predictor of pain crises in this sample of patients. None of the other hematological variables were significant predictors of disease severity in this study. The strong relationship between %HbF and disease severity identified in this study suggests that a single %HbF measurement may be useful in predicting important aspects of the clinical course of children with sickle cell anemia.
De novo X;Y translocation associated with imperforate anus and retinal pigmentary abnormalities
Authors: Johnston Kathreen , Schonberg Steven , Littman Victoria , Gregory Teresa , Gelbart Samuel , O'Donnell James , Cox David R. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractCytogenetically detectable translocations of Y chromosome material onto the distal short arm of an X chromosome are rare and result in a variable and poorly defined phenotype of short stature and short limbs occasionally associated with mental retardation. We report on a patient with a de novo 46,X,t (X;Y) (p22;q11) chromosome constitution who has additional features not previously described with this chromosome abnormality, including abnormal retinal pigmentation, imperforate anus, and hydronephorosis. Our patient extends the phenotype associated with X;Y translocations, raising new considerations for the clinical management and genetic counseling of such patients and their families.
Segregation and linkage analyses of dopamine‐β‐hydroxylase activity in a six‐generation pedigree
Authors: Asamoah Alexander , Wilson Alexander F. , Elston Robert C. , Dalferes Edward , Berenson Gerald S. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractSerum dopamine‐β‐hydroxylase (DBH) levels and 30 polymorphic markers were determined on 178 individuals of the HGAR 29 family, ascertained through six probands who had clinical and electrocardiographic evidence of myocardial infarction. Individuals in this pedigree with a history of heart attack had significantly lower levels of DBH, but this difference was partly confounded with age differences. Pedigree segregation analysis showed evidence of a codominant gene for DBH segregating in the family. Linkage analysis between the putative DBH locus and 30 polymorphic marker loci, assuming a codominant model, yielded a largest lod score of 0.53, with ABO at 20% recombination. Adding this to the lod scores obtained by Elston et al [1979] and Goldin et al [1982], we obtain combined lod scores of 2.49 and 2.50 at 0.0 and 10% recombination respectively.
Delineation of the male phenotype in craniofrontonasal syndrome
Authors: Morris Colleen A. , Palumbos Janice C. , Carey John C. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe are reporting on a 4‐generation family in which 6 individuals had frontonasal dysplasia with variable extracranial abnormalities. All affected persons had hypertelorism, bifid or broad nose, and highly arched palate. Associated abnormalities included cleft lip and palate (1/6), webbed neck (2/6), Sprengel anomaly (2/6), pseudoarthrosis of the clavicle (2/6), pectus excavatum (3/6), narrow, sloping shoulders (3/6), diaphragmatic hernia (2/6), broad first toe (4/6), brachydactyly (3/6), fifth finger clinodactyly (5/6), longitudinal grooves of nails (5/6), shawl scrotum (2/3 males), first degree hypospadias (1/3), and mild mental retardation (1/6). Only one affected female had brachycephaly and right coronal synostosis. Four other affected relatives had varying degrees of facial asymmetry, but normal skull contour. No male to male transmission is observed, and both daughters of an affected male were affected. Based on the phenotype of the 3 affected females, craniofrontonasal syndrome (CFNS) is the likely diagnosis. However, there are 3 affected males in this kindred, and 2 of the 3 had significant anomalies. Affected males also had genital abnormalities and pectus deformity of the chest, not previously reported in this condition. Two of the 3 males have posterolateral diaphragmatic hernia. This family expands the phenotype of affected males.
Intrafamilial variability in lysosomal storage diseases
Authors: Zlotogora Joël , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractIn most lysosomal storage diseases clinical variability is found and affects age‐of‐onset, severity, and the degree of neurological involvement. Very often the variability is due to the existence of different mutations leading to the same enzyme deficiency. In most of the families with more than one person affected, the clinical picture is very similar. Intrafamilial variation has been reported in the lysosomal storage diseases related or not related to genetic heterogeneity. In families in which different affected persons have the same genotype, as in X‐linked disorders, or autosomal recessive diseases in which both parents of the affected sibs are carriers and healthy, the variability must be due to factors not related to the genotype. On the other hand, when different mutations are present in the same family, the variability may be related to the differences in the genotype of the affected persons. Knowledge of the possibility of intrafamilial variability and its genetic basis is essential in clinical and prenatal diagnosis of the lysosomal storage diseases.
Do some patients with seckel syndrome have hematological problems and/or chromosome breakage?
Authors: Butler Merlin G. , Hall Bryan D. , Maclean Ronald N. , Lozzio Carmen B. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe report on a 12‐yr‐old female and a 14‐yr‐old male with Seckel syndrome. The 12‐yr‐old female had pancytopenia, which is seen occasionally in patients with Seckel syndrome and is also a feature of Fanconi anemia, a well‐recognized autosomal recessive dwarfism syndrome with chromosome instability. Chromosome breakage analysis of both of our patients also indicated chromosome instability. We suggest that there may be a subgroup of Seckel syndrome patients with chromosome instability and/or hematological problems.
Waardenburg syndrome, Hirschsprung megacolon, and Marcus Gunn ptosis
Authors: Meire F. , Standaert L. , De Laey J. J. , Zeng L. H. , Neri Giovanni 
Published: June 2005

AbstractA patient with Waardenburg syndrome type II associated with Hirschsprung megacolon and Marcus Gunn ptosis is presented. It is suggested that these different anomalies are manifestations of the same neurocrestopathy.
Chromosome 20 deletion in multiple endocrine neoplasia type 2: Expanded double‐blind studies
Authors: Babu V. Ramesh , Van Dyke Daniel L. , Flejter Wendy L. , Jackson Charles E. , Opitz John M. , Reynolds James F. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractMultiple endocrine neoplasia (MEN) type 2A and 2B are autosomal dominant syndromes in which medullary thyroid cancers are associated with adrenal pheochromocytomas. We have expanded our double‐blind studies of high‐resolution G‐banded chromosomes from lymphocytes to a total of 12 MEN‐2A families, 7 MEN‐2B (mucosal neuroma phenotype) families and 23 non‐MEN control subjects. Eighteen of 23 different control subjects were scored as having normal chromosomes 20, and 15 of 21 MEN‐2A and 4 of 8 MEN‐2B patients were scored as having an interstitial deletion: del(20) (p12.2p12.2). These findings suggest that the dominant mutation in many MEN‐2A and MEN‐2B families is a visible deletion within band 20p12.2. Combining the results of these double‐blind studies with those of the only other comparable reported double‐blind series provides a statistical probability of less than 1/1000 that the association between MEN‐2A and the deletion was observed by chance alone. However, the occasional discrepancies in classification using presently available techniques preclude the use of high resolution chromosome studies for the diagnosis of MEN‐2.
A major gene model for the familial aggregation of plasma IgA concentration
Authors: Asamoah Alexander , Wyatt Robert J. , Julian Bruce A. , Quiggins Patricia A. , Wilson Alexander F. , Elston Robert C. , Reynolds James F. 
Published: June 2005

AbstractPlasma IgA concentration was determined on 94 individuals of an eastern Kentucky family (IGAN1) with some members having clinical and biopsy‐proven IgA nephropathy, and on 197 individuals of a large Louisiana family (HGAR29) with no clinical history of IgA nephropathy but on whom 30 polymorphic markers had previously been typed. Pedigree segregation analysis was used to fit a major gene model, and a moderately large lod score for linkage to the ABO locus (1.50 at 0% recombination) suggested the existence of a recessive allele for high plasma IgA concentration. This allele is only slightly more prevalent in pedigree IGAN1 than in pedigree HGAR29, indicating that it is a minor, rather than a major, etiologic factor in IgA nephropathy.
Osteogenesis imperfects type III: An ancient mutation in Africa?
Authors: Viljoen Denis , Beighton Peter , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractIn a survey of institutions for crippled persons in Zimbabwe, 58 patients with osteogenesis imperfecta (OI) were identified; 42 had the rare OI Type III. The Shona and Ndebele people, who comprise the major tribal groups in Zimbabwe, both had a similar and relatively high gene frequency for this disorder. Both tribes were derived from common progenitors, but until 150 years ago had been geographically separated for 2 millenia. Subsequently, they have remained culturally and socially distinct. The implications are that the mutation for OI III in Africa occurred at least 2,000 years ago.
New autosomal dominant branchio‐oculo‐facial syndrome
Authors: Fujimoto Atsuko , Lipson Mark , Lacro Ronald V. , Shinno Nancy W. , Boelter William D. , Jones Kenneth L. , Wilson Miriam G. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe observed an autosomal dominant disorder of abnormal upper lip, which resembles a poorly repaired cleft lip, malformed nose with broad bridge and flattened tip, lacrimal duct obstruction, malformed ears, and branchial cleft sinuses and/or linear skin lesions behind the ears in several persons in 3 families. In each of the 3 families, an affected parent had at least one affected child. Father‐to‐son transmission in one of these families ruled out X‐linked inheritance. Other anomalies include coloboma, microphthalmia, auricular pits, lip pits, highly arched plate, dental anomalies, and subcutaneous cysts of the scalp. Premature graying of hair occurred in the affected adults. Growth retardation, developmental delay, and hand anomalies are variable components of the syndrome.
The Nager syndrome
Authors: Hecht Jacqueline T. , Immken LaDonna L. , Harris Lileah F. , Malini Srini , Scott Charles I. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThe Nager syndrome was identified in a newborn infant and in a subsequent sib by prenatal ultrasonography. This report documents an autosomal recessive pattern of inheritance for this disorder.
Neu‐Laxova syndrome: Report of a case and comments
Authors: Karimi‐Nejad Mohammad Hassan , Khajavi Hooshang , Gharavi Mohammad Jafar , Karimi‐Nejad Roxana , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe report on an infant with Neu‐Laxova syndrome [Neu et al, 1971; Laxova et al, 1972; Povysilova et al, 1976; Lazjuk et al, 1979; Scott et al, 1981; Fitch et al, 1982; Mueller et al, 1983; Turkel et al, 1983; Paes et al, 1985], and emphasize the ichthyotic skin lesions as a prominent characteristic change in this syndrome and as the probable cause of some of the other findings. Also, we call attention to the increased fatty tissue beneath the epidermis and the atrophic muscles there embedded. These findings should be considered in the diagnosis of this syndrome.
Twinning, nonrighthandedness, and fusion malformations: Evidence for heritable causal elements held in common
Authors: Boklage Charles E. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractCertain relatively common congenital malformations that are reported to be excessive in frequency among twins are also found in excess among first‐degree relatives of twins. They are familially associated with each other. Like twinning, they are familially associated with nonrighthandedness (NRH). They also share the fact that they affect structures that are built by the fusion of bilateral embryonic halves and then remodeled under the influence of neural crest mesenchyme. This conjunction of associations suggests that twinning, NRH, and the fusion malformations share causal elements, some of which may be heritable. Determination of spatial relationships in embryogenesis (“embryonic body symmetry determination”) and the functions of neural crest mesenchyme may be mechanisms unifying these effects.
Goldenhar complex in discordant monozygotic twins: A case report and review of the literature
Authors: Boles Debra J. , Bodurtha Joann , Nance Walter E. , Reynolds James F. 
Published: June 2005

AbstractIn 1952, Goldenhar described a pair of monozygotic twins who were discordant for epibulbar dermoids, auricular appendages, malformations of the auricle, and hemifacial microsomia. Eighteen twin pairs have subsequently been described in which at least one member exhibited these manifestations. We report on an additional pair of discordant dichorionic monozygotic male twins. All of the 5 monozygotic twin pairs for which placental information is available have been discordant and 2 of these had dichorionic membranes. The failure of discordant monozygotic twins to be limited to monochorionic pairs argues against the hypothesis that developmental abnormalities arising from the placental vascular anastomoses that are commonly found in monozygotic twins is the probable explanation for the discordant expression of these traits in twins.
Gonadal mosaicism in pseudoachondroplasia
Authors: Hall Judith G. , Dorst John P. , Rotta Julie , McKusick Victor A. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe report on a family in which a brother and sister have pseudoachondroplasia and normal parents. The brother married a normal woman, and they have 2 daughters; one of them has typical changes of pseudoachondroplasia, the other is normal. The most likely explanation in this family is gonadal (germinal cell) mosaicism in one of the grandparents. Other reports of possible autosomal recessive pseudoachondroplasia are reviewed. It is likely that gonadal mosaicism is responsible for a small percentage of cases with what appears to be a new mutation for pseudoachondroplasia.
Recurrence risks in the presence of single gene susceptibility to environmental agents
Authors: Khoury Muin J. , Beaty Terri H. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractInvestigators often attribute the 2‐5% sibling recurrence risks of common congenital malformations to a multifactional/threshold model (MFT) mechanism. However, most studies fail to address adequately the role of specific environmental factors and their interaction with genetic factors in recurrence risks. We consider the effects of a hypothetical environmental agent on recurrence risks in the presence of a single gene‐mediated differential susceptibility. It can be shown that recurrence risks increase with increasing population exposure frequency to the agent and the strength of gene‐environment interaction (relative risk among susceptible genotypes). However, they are usually much lower than expected on the basis of simple Meridelian segregation. Moreover, recurrence risks decline considerably between 1st, 2nd, and 3rd degree relatives, especially for recessive traits. Because single gene‐mediated differen‐tial susceptibility can mimic the MFT model in many instances, family studies of malformations (and other common diseases) could be more rewarding if they incorporate in their design and analyses specific environmental exposures affecting disease risk.
Decreased cell viability of fibroblasts from two patients with a ring chromosome: An in vitro reflection of growth failure?
Authors: Kosztolányi György , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe found decreased cell viability in fibroblast cultures from two patients, one with ring chromosome 4, the other with ring chromosome 15, who had severe somatic retardation. Cell viability was studied with the trypan blue exclusion assay, and in comparison with matched control cells was found to be 72.0 vs. 93.1%, and 79.8 vs. 90.2%, respectively. Cloning efficiency of fibroblasts from the patient with ring chromosome 15 was also decreased (12.3 vs. 25.7%). It is suggested that the decreased cell viability is due to a continuous production of hypomodal cells, a process related to the ring structure per se, and perhaps responsible for the severe somatic retardation frequently observed in patients with a ring chromosome.
Further delineation of the 3‐M syndrome with review of the literature
Authors: Hennekam Raoul C. M. , Bijlsma Jan B. , Spranger Jürgen , Neri Giovanni 
Published: June 2005

AbstractThe 3‐M syndrome is a clinically recognizable disorder characterized by prenatal and postnatal growth retardation and a spectrum of consistent minor anomalies. Intelligence seems normal. Inheritance is probably autosomal recessive, with possible expression of the mutant gene in the heterozygote. Three sibs with the 3‐M syndrome are reported, together with an extensive review of the pertinent literature.