bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acro‐renal‐ocular syndrome: Autosomal dominant thumb hypoplasia, renal ectopia, and eye defect
Authors: Halal Fahed , Homsy Magda , Perreault Giiles 
Published: June 2005

AbstractSeven individuals from 3 generations of a French‐Canadian family had various combinations of acral, renal, and ocular defects. Acral anomalies varied from mild hypoplastic distal portion of the thumbs, with limited motion at IP joint, to severe thumb hypoplasia and preaxial polydactyly. Renal anomalies varied from mild malrotation to crossed renal ectopia without fusion; other urinary tract anomalies were vesicoureteral reflux and bladder diverticula. Ocular manifestations varied from complete eye coloboma, coloboma of the optic nerve, ptosis, and Duane anomaly. The syndrome seems to be an autosomal dominant trait with high penetrance and variable expressivity. Dermatoglyphics were abnormal; in addition to a triradius t' present in all, some also had various combinations of high TRC, thenar exit of A line, and rare patterns in interdigital area IV.
The bingo model of survivorship. II: Statistical aspects of the bingo model of multiplicity 1 with application to hereditary polyposis of the colon
Authors: Morales Arlene Joan , Murphy Edmond A. , Krush A. J. , Optiz John M. 
Published: June 2005

AbstractSome Mendelian disorders (Huntington chorea, hereditary polyposis coli) are not manifest at birth show a distribution in the age of onset. Patients at risk fall into three groups. In type I, they are affected when first examined. In type II, they are not affected at one visit, but are at a later visit. Those of type III (who comprise an indistinguishable mixture of those who have, and those who have not, inherited the gene) are never found to be affected. This paper posits a model that the age of onset is logistic. (It is a degenerate bingo model in which competing causes of death may be ignored.) The statistical properties of maximum likelihood estimation (MLE) are explored by Monte Carlo simulation of this logistic function with known arbitrary parameters. Two schemes are used: point‐prevalence (or synchronic) data of types I and III, and piecewise longitudinal (diachronic) data; this allows all three types to be included. Samples of various sizes between 25 and 100 are used. While estimates of the parameters are positively biased (especially with small samples), the estimate of the mean appears to be consistent, almost unbiased, and fairly precise, though somewhat larger than the estimates from the lower bound (a fact that calls for some caution in interpreting actual data). The MLE was applied to 109 patients with the Gardner syndrome (GS); measures of variability found by applying MLE to four random subsets of 25 each were compared against the asymptotic estimates. The analysis was also applied to 36 persons with familial polyposis coli (FPC). The mean age of onset in GS and FPC was similar, and since they are rather earlier than is currently believed, it is recommended that regular supervision be started at not later than 10 years of age.
Lethal multiple pterygium syndrome in an 18‐week fetus with hydrops
Authors: Isaacson Glenn , Gargus J. Jay , Mahoney Maurice J. , Optiz John M. 
Published: June 2005

AbstractWe present the case of an 18‐week abortus with lethal multiple pterygium syndrome and hydrops. Radiographic and anatomic study showed none of the bony abnormalities reported in live‐born children with multiple pterygium syndrome. The pathogenesis of the hydrops was not apparent. The findings of cleft palate, pulmonary hypoplasia, muscular atrophy, gracile thoracic bones, and fetal death are typical of the lethal variant.
The Bartsocas‐Papas syndrome: Autosomal recessive form of popliteal pterygium syndrome in a male infant
Authors: Papadia Francesco , Zimbalatti F. , La Rosa C. Gentile 
Published: June 2005

AbstractWe report on an additional patient with the severe autosomal recessive form of the popliteal pterygium syndrome. The patient was diagnosed at birth and had all of the phenotypic manifestations of this rare syndrome. Clinical findings and natural history suggest this is a distinct genetic entity.
A Genetic Study of red cell osmotic fragility in Huntington's disease
Authors: McCormack Michael K. , Lazzarini Alice , Toke David , Lepore Frederick 
Published: June 2005

AbstractThe erythrocyte osmotic fragility was evaluated on 19 unmedicated subjects with Huntington's disease and 42 individuals at 50% risk, 27 children at 25% risk, and a group of 60 hematologically normal control persons. Five older subjects at 50% risk for Huntington's disease as well as 6 Alzheimer's disease individuals were also evaluated for comparison.The osmotic fragility of fresh and 24‐hour incubated red cells was analyzed and a fragility index calculated for each individual. The fragility index for the Huntington's disease group was statistically lower than that of the control group (P < .001) suggesting that the Huntington's disease erythrocytes had a reduced osmotic fragility. In the 50% risk group, 45% of the subjects demonstrated decreased osmotic fragility and 55% had normal fragility. For those subjects in the 25% risk group, 22.2% had decreased fragility and 77.8% had normal fragility. Twenty‐seven offspring were evaluated of the 14 persons at 50% risk for Huntington's disease with children; eight of the 14 individuals at 50% risk showed normal fragility and all 16 of their children showed fragility indices with the normal range. The remaining six persons at 50% risk for Huntington's disease had increased erythrocyte fragility and out of their 11 children, five showed normal fragility and six had decreased fragility.These data support the hypothesis of reduced erythrocyte osmotic fragility in individuals affected with and at risk for Huntington disease, and demonstrate the need of further study of the erythrocyte in this complex behavioral genetic disease.
Age at clinical onset and at ultrasonographic detection of adult polycystic kidney disease: Data for genetic counselling
Authors: Bear J. C. , McManamon P. , Morgan J. , Payne R. H. , Lewis H. , Gault M. H. , Churchill D. N. , Opitz John M. 
Published: June 2005

AbstractFew reports are available on the age‐related risk of relatives of affected persons to manifest adult polycystic kidney disease (APKD). For 371 persons in 17 kindreds, at risk for APKD by virtue of having an affected first degree relative, we calculated the estimated probability of clinical diagnosis of APKD to be 0.011 by age 20, 0.041 by age 30, 0.115 by age 40, 0.299 by age 50, and 0.404 by age 60 years (expected = 0.50). Ultrasonographic examination of 172 asymptomatic persons at risk showed definite APKD is 60. The probability of ultrasonographic detection of asymptomatic APKD is estimated as 0.222, 0.657, and 0.855 at age 5, 15, and 25 years, respectively. The probability of having APKD following normal ultrasonogram results (conservatively assuming 90% specificity) is estimated as 0.46, 0.28, and 0.14 for persons at 50% risk in their first, second, or third decade. The marginal benefit of ultrasound as a diagnostic test for APKD for persons in the second or third decade is estimated as 0.37 and 0.41, respectively for a “positive” test and 0.22 and 0.37 for a “negative” test.
Corneal changes, hyperkeratosis, short stature, brachydactyly, and premature birth: A new autosomal dominant syndrome
Authors: Stern Judith K. , Lubinsky Mark S. , Durrie Daniel S. , Luckasen John R. , Opitz John M. 
Published: June 2005

AbstractWe report on an autosomal dominant syndrome consisting of unique corneal epithelial changes, diffuse palmoplantar hyperkeratosis, distal onycholysis, brachydactyly, short stature, premature birth, and dental problems. This condition has been present in seven persons in three generations of one family. Corneal biopsies demonstrate mild dysplastic changes in the epithelium. Skin biopsies show hyper‐keratosis and acanthosis. In both eye and skin specimens, results of stains for polysaccharides, amyloid, and tyrosine were unremarkable.Roentgenograms of the hands show short distal phalanges, short 4th metacarpals, and constriction of the heads of some of the metacarpals. In three of four affected relatives, a variable medullary narrowness is seen. In mode of inheritance, clinical appearance, and/or assoicated defects. This syndrome appears to differ from previously reported conditions that include palmoplantar hyperkeratosis and/or corneal changes.
Forearm fullness in Coffin‐Lowry syndrome: A misleading yet possible early diagnostic clue
Authors: Hersh Joseph H. , Weisskopf Bernard , DeCoster Crystal , Opitz John M. 
Published: June 2005

AbstractTwo unrelated infants with delayed development and suspected abnormalities of the upper limbs were found to have the Coffin‐Lowry syndrome. Both had marked fullness of the forearms in the presence of normal skeletal structures which resulted from increased subcutaneous fat. Although initially misleading, the forearm changes may serve as an early diagnostic clue in this disorder.
Prenatal diagnosis of asphyxiating thoracic dysplasia
Authors: Lipson M. H. , Waskey J. , Rice J. , Adomian G. , Lachman R. , Filly R. , Rimoin D. , Opitz John M. 
Published: June 2005

AbstractA fetus at risk for asphyxiating thoracic dysplasia was studied with ultrasound examination at 16, 18, and 23 weeks of pregnancy. Definite shortness of fetal femora was observed. Radiographic and histologic examinations after pregnancy termination confirmed the diagnosis. Asphyxiating thoracic dysplasia appears to be one of an increasing number of skeletal dysplasias that can be diagnosed prenatally with ultrasound.
Serum myoglobin in Duchenne muscular dystrophy carrier detection: A comparison with creatine kinase and hemopexin using logistic discrimination
Authors: Percy Maire E. , Pichora Geoffrey A. , Chang Lebe S. , Manchester Kathryn E. , Andrews David F. , Opitz John M. 
Published: June 2005

AbstractLogistic discrimination was used to assess the effectiveness of serum myoglobin (Mb), creatine kinase (CK), and hemopexin (H) measurements in identifying Duchenne muscular dystrophy (DMD) carriers. Subjects included 36 obligate carriers, 46 age‐matched control women, 30 mothers of isolated cases, and 14 DMD patients. The percentages of obligate carriers with logistic carrier probabilities exceeding the upper normal 95th centile (or 97.5th centile) were: CK alone, 63% (50%); Mb alone, 65% (62%); CK and Mb, 66% (62%); CK and H, 78% (65%); CK H and Mb, 72% (65%). In this study, Mb identified more carriers than CK at the 97.5% level, but there was no advantage in using Mb measurements with CK. CK provided slightly better overall separation of the control and carrier groups than Mb. CK, Mb, and H in combination provided significantly better separation than CK and H, or CK alone.
A molecular method for detecting the presence of the human Y chromosome
Authors: Friesen Helena , Nishioka Yutaka , Opitz John M. 
Published: June 2005

AbstractThe presence of the human Y chromosome can be inferred from the detection of a male‐specific 3,4‐Kb band generated by digestion with the restriction enzyme Hae III. However, direct visualization of this band is sometimes difficult owing to high background of DNA fragments common to both sexes, and Y chromosome length polymorphism. We have shown that the 3.4‐Kb band can be detected by filter hybridization to a large DNA fragment (> 20 Kb) also generated by Hae III digestion. Since this large DNA fragment is easily isolated from either sex, it should prove useful to determine sex when chromosome analysis is impractical.
Inherited metabolic myopathy with storage of glycoproteins and glycosaminoglycans
Authors: Ionasescu Victor , Pedrini Victor , Aschenbrener Carol , Ionasescu Rebeca , Searby Charles 
Published: June 2005

AbstractTwo related patients (mother and daughter, ages 28 and 5 years) showed mild to moderate weakness and atrophy of facial and shoulder muscles with congenital onset and minimal progression. Serum creatine kinase was elevated in the child. Muscle biopsy showed normal light‐microscopic and histochemical findings, but scattered sarcoplasmic vacuoles with storage of granular material were evident on electron microscopy. Storage of granular material was also identified in fibroblasts which were weakly PAS‐positive, stained metachromatically with toluidine blue and orthochromatically with alcian blue. Muscle glycogen values were lownormal. Repeated biochemical studies of cultured fibroblasts identified excessive storage of glycosaminoglycans and glycoproteins. The uptake of 3H‐glucosamine in cultured fibroblasts was 1.7–3.4 times greater in the patients than in control individuals, while the rate of turnover of the radioisotope was normal. These findings suggest that the genetic defect in this inherited metabolic myopathy is related to excessive synthesis of glycosaminoglycans and glycoproteins.
Inbreeding effect on morbidity: II. Analyses of a third survey including and excluding infant‐juvenile mortality among Brazilian whites and Negroes
Authors: Elisbão T. , Freire‐Maia N. 
Published: June 2005

AbstractData on a survey involving 10,458 liveborn white and nonwhite (mulattoes and Negroes) persons have been analyzed to estimate B, A, and B/A for anomalies in general, both including and excluding infant‐juvenile mortality. In both instances and race groups, the approximate estimates of those parameters were 0.5, 4.5, and 12. Inbreeding seems to disclose a predominantly mutational load.
Inbreeding effect on morbidity: III. A review of the world literature
Authors: Freire‐Maia N. , Elisbão T. , Opitz John M. 
Published: June 2005

AbstractA review of the international literature on the inbreeding effect on morbidity is presented. For anomalies in general, the estimates of B vary from 0.2 to 5.8, of A from 0.01 to 0.23, and of B/A from 3 to 77. The respective modal estimates are roughly around 0.5, 0.03, and 20. A review of the estimates for specific anomalies also shows a wide range of values: from B = 0.0008, A = 68 × 10−8, and B/A = 1,176 (for acheiropodia) to B = 2.9, A = 0.24, and B/A = 12 (for “incapacity for military service”). Some estimates of B/A lower than 12 have been obtained for congenital malformations in some countries. An overall analysis of the whole body of data suggests that most of the anomalies are either entirely or predominantly mutational in origin.
Effects of consanguineous marriages on morbidity and precocious mortality: Genetic counseling
Authors: Freire‐Maia Newton , Opitz John M. 
Published: June 2005

AbstractThe excess risks of morbidity and precocious mortality for the offspring of incestuous matings and of matings of uncles‐nieces and aunts‐nephews, first cousins, first cousins once removed, and second cousins have been estimated as 32%, 18%, 9%, 5%, and 2.5%, respectively. These estimates are based on the theory of Morton et al [1956], assuming a damage (genetic and nongenetic) of 20% for the offspring of nonconsanguineous couples and two “deleterious” equivalents per gamete. Other possibilities (a damage of 40%; 2.5 deleterious equivalents per gamete), a partition of the total risk into prenatal and postnatal events, and some aspects of the inbreeding theory are also presented. Comments intended for persons interested in counseling are provided.
Potential impact of a predictive test on the gene frequency of Huntington disease
Authors: Schoenfeld Miriam , Myers Richard H. , Berkman Barbara , Clark Eleanor 
Published: June 2005

AbstractFifty‐five individuals at 50% risk of inheriting Huntington disease (HD) were given in‐depth structured interviews to survey attitudes toward use of a predictive test and to assess the possible impact of such a test on the number of gene carriers born. Three‐quarters of the sample said they would take predictive test. Given a positive predictive or prenatal test, the number of individuals choosing to have children is reduced from 80% of the total sample to 42%, or by almost one‐half. The large proportion of at risk individuals who say they would use a predictive test underscores the importance of developing guidelines for its administration prior to implementation.
A bivariate problem in human genetics: Ascertainment of families through a correlated trait
Authors: Dawson Deborah V. , Elston Robert C. , Opitz John M. 
Published: June 2005

AbstractIn genetic analysis of pedigree data, nonrandom sampling occurs commonly and appropriate adjustments for the ascertainment procedure are necessary for the correct interpretation of results. In this paper we consider ascertainment models for the situation in which proband selection is made on the basis of one trait, but the desired object of analysis is another related trait for which the individuals in the pedigree also are measured. The ascertainment function corresponding to the most useful bivariate form, that involving two correlated quantitative traits, is described explicitly under suitable assumptions. As its form is mathematically intractable for purposes of pedigree analysis, an approximation is developed. Such ascertainment models accomplish corrections for ascertainment while permitting adjustment for covariates, analysis of traits correlated with the trait used in selection, and multivariate analysis of nonrandomly sampled pedigrees using linear combinations of traits.
Isoelectric focusing of serum in genetic counselling of families with cystic fibrosis
Authors: Super Maurice , Swindlehurst Christine 
Published: June 2005

AbstractThe high incidence of carriers of cystic fibrosis in the general population allows application of a less than perfect test to genetic counselling of relatives of children with the disorder and their spouses. In the absence of a definitive carrier detection test, we employ isoelectric focusing of serum in this way and include the a priori chance of carrier status in calculating the risk. The test will eventually be replaced but for the present is preferable in our hands to counselling based simply on the known gene frequency.
Constitutive fragile sites 1p31, 3p14, 6q26, and 16q23 and their use as controls for false‐negative results with the fragile(X)
Authors: Daniel Art , Ekblom Linda , Phillips Sandra , Opitz John M. 
Published: June 2005

AbstractFragile(X) estimations in fragile(X)‐mental retardation hemizygotes or heterozygotes can become falsely negative in stored blood (lymphocytes). This was shown in blood stored (before culture) at 4°C, room temperature (25°C), 37°C, and 39°C for 1–4 days. After storage, blood was cultured in Ham's F10‐5% FC serum with 0.1 μM FUdR and scored for fra(X) and the constitutive fragile sites at 3p14 and 6q26. It was found that the proportion of cells expressing the fragile(X) and the 3p14 site varied inversely with the temperature and time of storage. In addition, 50 patients and controls were scored for the three latter sites after routine 72–96‐hr culture in F 10–0.05 or 0.1 μM FUdR. The 3p14 site was detected in every individual tested in a mean ± S.D. of 11.3 ± 3.2% of cells (0.1 μM FUdR). It was found that this site was FUdR dose dependent whereas the 6q26 site was not. The 3p14 (but not the 6q26) site is therefore suitable as a control site for the FUdR effect. It is proposed that repeat studies are necessary when less then 4% 3p14 sites are present in specimens from males referred for fra(X) estimation. Other constitutive fragile sites (eg, 1p31 and 16q23) can also be used.
Apparent allelism of the hurler, scheie, and hurler/scheie syndromes
Authors: Mueller O. Thomas , Shows Thomas B. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThe Hurler, Scheie, and Hurler/Scheie syndromes are clinically distinct disorders due to inherited deficiencies of lysosomal α‐iduronidase activity. The genetic relationship of these disorders was investigated by complementation analysis using a heterokaryon enrichment procedure. Fusions between fibroblasts derived from Hurler, Scheie, or Hurler/Scheie subjects in any combination resulted in no detectable correction of α‐iduronidase activity, indicating that they form a single complementation group. Control fusions between these fibroblasts and mucolipidosis II or III cells, which are also α‐iduronidase deficient due to an enzyme processing defect, resulted in restoration of up to 57% of normal α‐iduronidase activity. These results also suggest allelism of the Hurler, Scheie, and Hurler/Scheie syndromes. However, the genetic make‐up of the Hurler/Scheie syndrome was not resolved.
Prenatal diagnosis of Meckel syndrome: Case reports and literature review
Authors: Johnson Virginia P. , Holzwarth David R. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe report on 2 couples at risk to have Meckel syndrome (MS) offspring. Three pregnancies were monitored by ultrasonography and alpha‐fetoprotein (AFP) assay in midtrimester. Of the 2 involving an affected fetus, one was thought to be unaffected.A literature survey was undertaken. Sources of error seem to lie in the heterogeneity of clinical manifestations and the variable onset and rate of progression of clinical components of MS and limitations in ultrasonographic resolution inherent in the scanner or due to the associated oligohydramnios.The following observations/suggestions are made concerning the prenatal diagnosis of MS: 1) Utilize as many tests as are available. 2) Amniotic fluid AFP is more likely to show significant elevation than serum AFP. 3) Ultrasonography should concentrate on presence of oligohydramnios, small head diameter, cystic mass at the occiput, large kidneys, and absent bladder. 4) Use serial AFP and sonographic examination if findings are initially normal or equivocal.
Presumed homozygous Ehlers‐Danlos syndrome type I in a highly inbred kindred
Authors: Kozlova S. I. , Prytkov A. N. , Blinnikova O. E. , Sultanova F. A. , Bochkova D. N. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWhile studying an extended family of individuals with the Ehlers‐Danlos (ED)syndrome type I, we found an affected male who was born to 2 affected consanguineous parents. This man had a more severe condition than that of his other affected relatives. Moreover, all 6 of his children were affected. Taking the pedigree data into account, the conditional probability of homozygosity for the ED gene in that patient was calculated as 97%. Some problems of the clinical and genetic approach to the recognition of the homozygous state in the ED syndrome are discussed using this family as an example.