bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paradoxical fixation of deleterious alleles in two‐locus systems with epistasis
Authors: Trojak Joseph E. , Murphy Edmond A. 
Published: June 2005

AbstractThe dynamics of four deterministic models of interaction between two Mendelian loci are explored numerically. At one locus there are two hypostatic alleles: h, the wild type and H, a deleterious mutant that in either heterozygous or homozygous state (depending on the specifics of the model) produces an abnormal phenotype. At another arbitrarily linked epistatic locus there are two alleles: e, the wild type with no effect on the expression of the H locus, and E, an epistatic mutant that in heterozygous or homozygous state (again, depending on the specifics of the model) blocks the expression of H. The parameters are the initial gamete frequencies, the recombination fraction, the genotypic viabilities, and the forward and back mutation rates at each locus. The He haplotype is eventually eliminated (unless back mutation occurs) from the population. If mutation is ignored, the evolutionary outcome is determined by the initial gamete frequencies and is either (1) an edge equilibrium comprising one pair of haplotypes only (he and He, or he and hE, or hE and HE, or He and HE, or, if there is no recombination, he and HE or hE and He); or (2) a corner equilibrium consisting of a single gametic type. Given that the forward mutation rates at both loci are greater than the back mutation rates, then the outcome is always the corner equilibrium in which HE is universal (apart from transient perturbations by mutation). In the process of fixation, the phenotypic impact of the deleterious allele H becomes neutralized by the epistatic allele E. The rate at which the initially harmful gene replaces the wild type gene depends on the recombination fraction, the genotypic viabilities, and the mutation rates.
Phenotypic heterogeneity in neural tube defects: A clue to causal heterogeneity
Authors: Martin R. A. , Fineman R. M. , Jorde L. B. , Opitz John M. 
Published: June 2005

AbstractWe report here retrospective data on 991 liveborn and stillborn infants with neural tube defects (NTDs) born to Utah residents from January 1, 1940 to December 31, 1979. Data were obtained from multiple sources including approximately 1.25 million vital statistics records and several hundred physician and hospital charts. Causal heterogeneity among NTD patients is presumed because 6% of our cases have other congenital anomalies not part of the NTD field defect. A significant association of NTDs with oral clefts is noted. Sex ratios and empiric recurrence risks for isolated NTDs and NTDs associated with other major malformations are also calculated.
Benign familial neonatal‐infantile seizures
Authors: Kaplan Robert E. , Lacey Daniel J. , Opitz John M. 
Published: June 2005

AbstractWe report on an autosomal dominant neonatal‐infantile seizure disorder and offer criteria for establishing the diagnosis and guidelines for the evaluation and treatment of this disorder. Long‐term anticonvulsant treatment usually is not required. The subsequent risk of a recurrent seizure disorder depends on whether other affected relatives developed a seizure disorder later in life. This disorder may have at least two different neonatally indistinguishable forms: one having an increased empiric risk (20%) of subsequent epilepsy, and a second which carries no increased risk. These familial neonatal‐infantile seizures are termed “benign” since they are not associated with subsequent psychomotor retardation.
Acrofacial dysplasia resembling geleophysic dysplasia
Authors: Spranger J. , Gilbert E. F. , Flatz S. , Burdelski M. , Kallfelz H. C. 
Published: June 2005

AbstractWe report on a 12‐year‐old girl with acrofacial dysplasia, growth retardation, joint contractures, mitral valve incompetence and focal hepatic storage of material reacting histochemically as glycoprotein. The patient's phenotype resembles that of patients with geleophysic dysplasia but differs with respect to facial appearance, milder changes of hand bones and normal capital femoral epiphyses. It is undecided if her disorder is part of a wider phenotypic spectrum of geleophysic dysplasia or a different entity.
Impact of PKU on the reproductive patterns in collaborative study families
Authors: Burns Joan K. , Azen Colleen G. , Rouse Bobbye , Vespa Hazel 
Published: June 2005

AbstractFactors that relate to reproductive patterns in 129 families after the birth of a child with phenylketonuria (PKU) include birth order of the index child, age of the parents at the birth of the index child, and expressed intentions of the parents whether or not to have additional children. Factors that do not correlate with reproductive histories include knowledge of the genetic and metabolic nature of PKU, the relationship of PKU to mental retardation and special diet, parental upset about the diagnosis, sex of the affected child, parental IQ, religion, education, and social class.Correlations found related to the question, “Is PKU the reason you don't want more children?” include stress factors in family functioning, mother's upset with the diagnosis, father's concerns about being a carrier, sex of the child with PKU, and degree of knowledge about PKU.Many of the Collaborative Study clinics tend to be more concerned about the consequences of PKU on the family than on society, and feel that families should receive genetic counseling to determine their reproductive risks and future plans. Upon self‐report, many clinics declare their counseling to be either “completely nondirective” or making a “conscious effort to be nondirective”.
Gene dosage studies supporting localization of the structural gene for galactose‐1‐phosphate uridyl transferase (GALT) to band p13 of chromosome 9
Authors: Shih Ling Yu , Suslak Lorraine , Rosin Irit , Searle Bernard M. , Desposito Franklin 
Published: June 2005

AbstractA newborn male was diagnosed as having a duplication of distal 9p material by GTG banding analysis. Gene dose studies for galactose‐1‐phosphate uridyl transferase (GALT) were performed on the patient, his mother (the balanced translocation carrier), a 3‐year‐old 47,XY + 9p male control, a 30‐year‐old woman with mosaic trisomy 9p, a newborn female control infant with complete trisomy 9, and age‐matched chromosomally normal control individuals. The findings support previous evidence that the GALT locus is at band p13 of chromosome 9.
The split‐hand and split‐foot anomaly in a central African Negro population
Authors: Viljoen D. L. , Beighton P. 
Published: June 2005

AbstractThe split‐hand and split‐foot anomaly (ectrodactyly) was identified in five individuals of three generations of a kindred from a remote African Village; seven more were known to be affected in a further two generations. The malformations were confined to the hands and feet and inherited as an autosomal dominant trait with variable expression. Bilateral triphalangeal thumbs were present in three of the affected individuals.
Reproduction in XYY males: Two new cases and implications for genetic counseling
Authors: Grass F. , McCombs J. , Scott C. I. , Young R. S. , Moore C. M. 
Published: June 2005

AbstractWe present two children—one, 47, XY, + mar, and the other, 47, XY, +21. Both fathers were found to have a 47, XYY chromosome constitution. The initial assumption was that the fathers' aneuploid conditions contributed to those of the offspring. However, the derivation of the marker chromosome could be paternal, maternal, or postzygotic, and examination of polymorphic structures of the number 21 chromosomes of the child with Down syndrome and his parents suggested maternal derivation of the supernumerary 21. To explore further the reproductive risks of an individual with the XYY cónstitution, previous reports of reproductive performance and testicular histology are examined as are two theories which suggest XYY males may be at an increased risk of producing aneuploid progeny. Based on these reports, recommendations are made for testing XYY males prior to genetic counseling.
Possible causal heterogeneity in spina bifida cystica
Authors: Toriello Helga V. , Higgins James V. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractA study was performed to determine whether causal heterogeneity can be demonstrated among the nonsyndromal spina bifida cysticas based on the vertebral level of the defect. Two groups were compared, probands with defects at or above T 11, likely representing defects of neuralization, and probands with defects at or below T 12, likely defects of canalization. Differences between the two groups were found with respect to reproductive history and occurrence of other malformations. A high degree of concordance for the type of defect among affected sib pairs was also observed. These findings indicate that there is probably heterogeneity within the spina bifida cysticas based on the level of the defect.
Laryngeal cleft: Report of eight patients and a review of the literature
Authors: Tyler Donald C. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractEight cases of laryngeal cleft are presented and the literature on this topic is reviewed. Patients most frequently present with stridor, respiratory distress, or a history of choking while feeding. A number of cases are found at autopsy or surgery. Laryngeal cleft frequently is found associated nonspecifically with tracheoesophageal fistula, cleft lip and cleft palate, and congenital heart defects. Laryngeal cleft may be a component manifestation of several syndromes, eg, the G syndrome, and the Pallister‐Hall syndrome of congenital hypothalamic hamartoblastoma, hypopituitarism, imperforate anus, and postaxial polydactyly. Surgical treatment is successful in more than 50% of the reported cases, depending on the extent of the cleft. Cleft larynx is most likely a developmental field defect, occurring coincidentally with separation of larynx and esophagus and closure of the larynx.
Hypopituitarism and septooptic “dysplasia” in first cousins
Authors: Blethen Sandra L. , Weldon Virginia V. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractAlthough familial forms of hypopituitarism are known, to our knowledge familial septooptic “dysplasia” in association with hypopituitarism has not been reported. We describe two first cousins with panhypopituitarism, one of whom had septooptic dysplasia. We discuss the possibility that septooptic dysplasia‐hypopituitarism may be inherited as an autosomal dominant, or recessive, or multifactorial trait.
Sternal malformation/vascular dysplasia association
Authors: Hersh J. H. , Waterfill D. , Rutledge J. , Harrod M. J. E. , O'sheal S. F. , Verdi G. , Martinez S. , Weisskopf B. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractSternal defects associated with superficial craniofacial vascular lesions are rare. We report on two additional patients with a sternal cleft and cutaneous, craniofacial hemangiomata to emphasize that this unusual combination of findings represents a recognizable sternal malformation/vascular dysplasia association. In addition, internal vascular lesions were also identified in these individuals, in one instance involving the upper respiratory tract and in the other the viscera. Although the pathogenesis of these findings is unclear, an early disturbance affecting midline mesodermal structures leading to lack of complete fusion of lateral sternal bands and overlying cutaneous tissue, or deficient formation of a proposed medioventral unpaired structure which may be involved in the formation of the sternum, and persistence and proliferation of midline angioblastic tissue may be possible mechanisms during the sixth to ninth gestational weeks. To date, all but one of the 15 known cases have been sporadic and no teratogen has been identified as a cause for these clinical manifestations. The presence of this association should signal the need to search for potentially life‐threatening internal hemangiomata.
Smith‐Lemli‐Opitz syndrome‐type II: Multiple congenital anomalies with male pseudohermaphroditism and frequent early lethality
Authors: Curry Cynthia J. R. , Carey John C. , Holland Julie S. , Chopra Devinder , Fineman Robert , Golabi Mahin , Sherman Sanford , Pagon Roberta A. , Allanson Judith , Shulman Sally , Barr Mason , McGravey Vincent , Dabiri Cyrus , Schimke Neil , Ives Elizabeth , Hall Bryan D. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractIn 1964, Smith et al described a syndrome of microcephaly, growth and mental retardation, unusual facial appearance, syndactyly of toes 2 and 3, and genital abnormalities. Major structural malformations and early death have been uncommon in the many subsequent literature reports. We report on 19 infants with a phenotype we propose to call Smith‐Lcmli‐Opitz syndrome (SLOS)‐Type II, in which major structural abnormalities, male pseudohermaphroditism, and early lethality are common. Of these 19 patients, 18 had postaxial hexaclactyly, 16 had congenital heart defect, 13 had cleft palate, and 10 had cataracts. Unusual findings seen in those patients at autopsy included Hirschsprung “disease” in five patients, unilobatod lungs in six, large adrenals in four, and pancreatic islet cell hypciplasia in three. Comparison of our cases to 19 similar literature cases suggests the existence of a distinct phenotype that may be separate from SLOS as originally described. It is also inherited as an autosomal recessive, as documented by occurrence in one pair of sibs in this study and recurrence in three reported families.
The Johanson‐Blizzard syndrome: A second report of full autopsy findings
Authors: Moeschler John B. , Polak Mark J. , Jenkins Jesse J. , Amato R. Stephen S. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe report on a second patient with Johanson‐Blizzard syndrome with full autopsy. The findings are similar to those of the one other available case, but gross or fine CNS maldevelopment was not present; although small by weight, the brain showed no cytoarchitectural disturbance. Normal intellecutal development does occur in this syndrome and may relate to the variable effects of the deleterious gene on the developing CNS.
Mosaic trisomy 7 and renal dysplasia
Authors: Verp Marion S. , Amarose Anthony P. , Esterly John R. , Moawad Atef H. , Reynolds James F. 
Published: June 2005

AbstractTrisomy 7 was detected in umbilical cord cells cultured from a fetus with renal dysplasia. Skin fibroblasts were diploid. Because of a paucity of liveborn infants with full trisomy 7, the phenotype is noi well described; however renal anomalies appear to be common with trisomy 7.
DOOR syndrome (deafness, onycho‐osteodystrophy, and mental retardation): Elevated plasma and urinary 2‐oxoglutarate in three unrelated patients
Authors: Patton M. A. , Krywawych S. , Winter R. M. , Brenton D. P. , Baraitser M. , Neri Giovanni 
Published: June 2005

AbstractWe describe three further children with the DOOR syndrome (deafness, onycho‐osteodystrophy and mental retardation). A severe seizure disorder and character‐istic facial appearance are part of the syndrome. Fourteen similar cases including the present patients are now on record. Autosomal recessive inheritance is likely.An increased level of 2‐oxoglutarate in both plasma and urine has been found in our three patients. It is suggested there may be an inherited metabolic defect in this malformation syndrome.
Mental retardation, spasticity, and transverse limb defects
Authors: Zlotogora Joël , Reynolds James F. 
Published: June 2005

AbstractWe report on a mentally retarded boy with spastic paraplegia and a transverse defect of the left foot who was bora to consanguineous parents. This association of ectrodactyly, mental retardation, and spastic paraplegia was first reported by Jancar [1967].
Prenatal diagnosis of a dup(3p) with holoprosencephaly
Authors: Gillerot Yves , Hustin Jean , Koulischer Lucien , Viteux Vincent , Neri Giovanni , Opitz John M. 
Published: June 2005

AbstractThe prenatal diagnosis of dup(3p) was made in a female conceptus, the father being a known carrier of a balanced translocation t(3;10)(p21;q26). Interruption of pregnancy at 19 weeks showed a fetus with a holoprosencephaly field defect. Two other cases of dup(3p) have been observed in the same family. The malfor‐mations were different in each of the 3 patients, suggesting a considerable degree of variability of dup(3p).
Presymptomatic testing for Huntington chorea: Ethical and legal issues
Authors: Lamport Ann T. , Opitz John M. , Shaw Margery W. 
Published: June 2005

AbstractThe recently developed presymptomatic test for Huntington chorea presents ethical and legal issues relating to the interests of fiduciary and nonfiduciary third parties. The issues are examined, and the resulting dilemmas are evaluated with respect to ethical principles and to current law.
German syndrome in sibs
Authors: Lewin Susan O. , Hughes Helen E. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe present a male‐female sib pair born to Ashkenazi Jewish parents with “arthrogryposis,” hypotonia‐hypokinesia sequence and lymphedema. Of all the “arthro‐gryposis” hypotonia syndromes, the condition in these sibs appears to be most like that of the patients of German et al [1975] and the patient of Salmon [1978]. They appear to be the first sib pair with German syndrome, which suggests autosomal recessive inheritance. Three of the four known families with affected children have been Ashkenazi Jews.
Prenatal detection of intestinal obstructions, aneuploidy syndromes, and cystic fibrosis by microvillar enzyme assays (disaccharidases, alkaline phosphatase, and glutamyltransferase) in amniotic fluid
Authors: Morin Pierre R. , Melançon Serge B. , Dallaire Louis , Potier Michel , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractMicrovillar enzymes (disaccharidases, alkaline phosphatase, and γ‐glutamyltrans‐ferase) were assayed in amniotic fluid from pregnancies with normal and abnormal fetuses to determine their specificity and reliability for the prenatal detection of intestinal obstructions and cystic fibrosis. All fetuses with imperforate anus, duodenal atresia, jejuno‐ileal atresia, multiple intestinal atresia, or other forms of intestinal obstructions, with or without associated ventral wall defect or aneuploidy syndrome, showed diminished microvillar enzyme activities below the normal range of control amniotic fluid samples. The exclusively intestinal hydrolases maltase, sucrase, palatinase, and alkaline phosphatase were the most reliable and sensitive markers to detect intestinal obstructions whereas more widely distributed trehalase and γ‐glutamyltransferase activities were less sensitive. The combination of intestinal disaccharidase maltase, sucrase or palatinase and ALP assays is more accurate for prenatal diagnosis of CF than a combination of intestinal ALP and GGTF assays.
The dynamics of angular homeostasis: I. General principles
Authors: Murphy Edmond A. , Berger Kenneth R. , Opitz John M. 
Published: June 2005

AbstractA general model is proposed casting aspects of ontogeny in quantitative terms amenable to genetic analysis. Its primordial construct is a chain of cells (termed a “pursuer”) growing under the influence of a signal towards a fixed structure termed a “target.” There is provision for graduated correction of the direction of growth of the pursuer. The determinants of scale include the size of the cells and the distance from the target. The minimum number of parameters is two: the initial angle of growth; and the force of the correction of errors of direction. Both are potentially of genetic interest. The impact of variation in these factors on the path of growth is studied. These findings are readily translated into biological terms, notably in congenital defects of the heart. Besides the primordial purposes, there are other objectives to the process. Some membranes require free edges, or large curvatures, or circular arrays. These secondary qualities require that the cells never reach the target. The target then becomes simply a construction point: that is, while remaining a center of attraction, it is no longer a true goal. If, because of undercorrection, the cell line misses the target at the first pass, it assumes a permanent orbit about it. The orbit rapidly comes to lie on a circle, with a radius independent of the initial angle of growth but related to the cell size and the restoration constant. From this property, several kinds of structures other than a simple bridge may result, especially when a series of lines of growth together form a tissue: a cusp, a free‐floating membrane, or a circular membrane to fill a gap.
Mental retardation, deafness, skeletal abnormalities, and coarse face with full lips: Confirmation of the Fountain syndrome
Authors: Fryns Jean‐Pierre , Dereymaeker Annemie , Hoefnagels Margot , Van den Berghe Herman , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe describe 3 moderately to severely mentally retarded males (2 brothers and 1 isolated patient) with congenital deafness due to an anatomical inner ear anomaly, the same manifestations that were present in the 4 sibs reported by Fountain [1974]: skeletal abnormalities with broad, stubby hands and feet and hyperky‐phosis, and a peculiar “coarse” face with swelling of the subcutaneous tissue, particularly of cheeks and lips. According to the present observations early‐onset, generalized seizures can be added to the symptom complex of this autosomal recessive trait.
Distal arthrogryposis type II D in three generations of a Brazilian family
Authors: Pagnan Nina Amalia Brancia , Gollop Thomaz Rafael , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe report on three members of a Brazilian family with distal arthrogryposis type II D. This autosomal dominant trait was described by Hall et al [1982] and is characterized by scoliosis without associated vertebral anomalies and distal contractures.To the best of our knowledge, this family is the second literature report of distal arthrogryposis type II D.
Aryl sulfatase A deficiency in psychiatric and neurologic patients
Authors: Herska M. , Moscovich D. G. , Kalian M. , Gottlieb D. , Bach G. 
Published: June 2005

AbstractTwo hundred ninety‐five psychiatric and neurologic patients were randomly screened for aryl sulfatase A (ASA) activity in lymphocyte extracts. Two of these patients showed very low ASA activity, in the range of metachromatic leukodys‐trophy (MLD)‐affected patients. The residual activity in these low ASA patients showed normal enzyme behavior with regard to ASA kinetic features and the ability to catabolize 14C labeled sulfatide by intact fibroblasts Taking into account that approximately 3% of the general population are homozygous for the pseudo‐aryl sulfatase A gene and are clinically unaffected, the data obtained here indicate that the patients studied in this work, as well as most psychiatric patients reported in the literature with low ASA activity, represent the normal ASA polymorphism. Thus, the very low ASA activity patients are in fact homozygous for the pseudo‐deficient allele, which does not result in clinical abnormalities. The clinical symptoms in these psychiatric patients and probably other “variant” MLD patients are therefore not related to low ASA activity.