bluuebunny/crossref_metadata_2025_split huggingface dataset:
An autosomal dominant syndrome of characteristic facial appearance, preauricular pits, fifth finger clinodactyly, and tetralogy of fallot
Authors: Jones Marilyn C. , Waldman J. Deane , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThis report describes six relatives with a syndrome of mild prenatal‐onset growth deficiency, an altered craniofacial appearance, preauricular pits, and clinodactyly of the fifth finger; three had tetralogy of Fallot. The clinical impact of this condition appears to be related to the severity of the cardiac defect. Autosomal dominant inheritance is implied by the occurence of the disorder in three successive generations with documented male‐to‐male transmission. Recognition of this syndrome is important in counseling families regarding recurrence risk for tetralogy of Fallot.
Syndromes with lissencephaly. II: Walker‐Warburg and Cerebro‐Oculo‐Muscular syndromes and a new syndrome with type II lissencephaly
Authors: Dobyns William B. , Kirkpatrick Joel B. , Hittner Helen M. , Kretzer Frank L. , Roberts Richard M. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractLissencephaly (smooth brain) is an abnormality of brain development characterized by incomplete neuronal migration and a smooth cerebral surface. At least two distinct pathological types occur, each associated with several recognized syndromes. In this paper, we report on the clinical and pathologic manifestations of four additional patients and classify and delineate three separate disorders with type II lissencephaly. We also report on a previously undescribed abnormality in one of the four patients—dilated rough endoplasmic reticulum cisternae containing an unknown osmiophilic secretory product, probably a glycoprotein.
History and relevance of the Hutterite population for genetic studies
Authors: Hostetler John A. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThe social and cultural origins of the Hutterian Brethren, the most inbred population in North America, are described along with the characteristics that make the group useful for genetic studies. The Hutterites represent a closed population, with high levels of fertility and consanguinity. The group maintains a stable residence pattern and keeps extensive genealogic records. The uniform pattern of communal living, the existence of endogamous subgroups within the population, and an orderly design for colony fission facilitates comparisons rarely found in other accessible populations. This inbred population is useful for detecting new recessively inherited diseases, for advancing our knowledge of the effect of inbreeding, and for analyzing human chromosomal variation. Selected demographic and genetic studies are cited.
Morquio syndrome (MPS IVA) and hypophosphatasia in a Hutterite kindred
Authors: Lowry R. B. , Snyder F. F. , Wesenberg R. L. , Machin G. A. , Applegarth D. A. , Morgan K. , Carter R. J. , Toone J. R. , Holmes T. M. , Dewar R. D. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractA patient is described who has Morquio syndrome (MPS IVA). He is a member of the Hutterite Brethren and genealogic analysis discloses a high inbreeding coefficient for the proband. The proband's sibship is segregating two autosomal recessive disorders, ie, MPS IVA and infantile hypophosphatasia. Two other families each have one or the other of these diseases but not both. The three families are distantly related.
Hutterite cerebro‐osteo‐nephrodysplasia: Autosomal recessive trait in a Lehrerleut Hutterite family from Montana
Authors: Opitz John M. , Lowry R. Brian , Holmes T. Mary , Morgan Kenneth , Reynolds James F. 
Published: June 2005

AbstractWe are reporting on two Lehrerleut Hutterite sisters who have a syndrome of 1) congenital shortness with mild spondylorhizomelic dwarfism; 2) later failure to thrive, ie deceleration of weight gain presumably due to CNS‐based severe feeding problems; 3) a CNS defect, probably developmental (not biochemical) with normal prenatal brain growth but later deceleration from 50th to 2nd centile associated with severe mental retardation and decorticate disturbances of neurologic function; and 4) possible renal involvement with terminal nephrotic syndrome.This seems to be a previously undescribed pleiotropic autosomal recessive trait.
Congenital contractures, edema, hyperkeratosis, and intrauterine growth retardation: A fatal syndrome in hutterite and mennonite kindreds
Authors: Lowry R. B. , Machin G. A. , Morgan K. , Mayock D. , Marx L. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe present clinical findings in infants from three kindreds (two Hutterite and one Mennonite) with an apparently unique, fatal disorder. The major manifestations consist of severe intrauterine growth retardation, congenital contractures, and tense skin which is easily eroded. The skin is tightly drawn over the face, giving an abnormal appearance consisting of a narrow, pinched nose, small mouth, limited jaw mobility, and ectropion (in one). One infant had first‐degree hypospadias. Apart from this, there were no organ malformations and the infants did not have hydrops. Histologically, the skin showed hyperkeratosis. It is postulated that this is a tissue dysplasia and that all of the clinical effects are secondary. The disorder appears to be an autosomal recessive trait. The two Hutterite families are from different endogamous subdivisions. They are related as fourth cousins onceremoved and fifth cousins in multiple ways through the six nearest common ancestors of all four parents. There are 25 founders (11 couples and three individuals) who are common ancestors. We computed the probability of joint descent of the four alleles in each pair of parents and in a sample of Alberta Hutterite couples, assuming that each of the common founders in turn was the original carrier. For an allele from one particular founder couple, there is a relatively greater probability of identity by descent for each pair of parents than on the average for other couples of the same endogamous subdivision.
II. Clinical studies in a kindred with a kinetic LDL receptor mutation causing familial hypercholesterolemia
Authors: Bilheimer David W. , East Cara , Grundy Scott M. , Nora James J. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe have studied a family carrying a variant of the class 2 mutation of familial hypercholesterolemia (FH) in which there is unusual longevity and in which obligate heterozygotes did not express constant or statistically significant hypercholesterolemia. The heterozygotes have the same kinetic defect in the processing of low density lipoprotein (LDL) receptors in their fibroblasts and the reduced fractional catabolic rate for apoLDL that is characteristic of other patients with heterozygous FH. However, their plasma lipid and lipoprotein levels are not as strikingly abnormal because they have normal or near normal rates of apoLDL synthesis.
Deletion of the distal long arm of chromosome 1: A definable syndrome
Authors: Johnson Virginia P. , Heck Louis J. , Carter Guy A. , Flom Jon O. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractBased on analysis of 15 cases, there appears to be a characteristic facial appearance and pattern of associated malformations that would allow clinical delineation of deletion of the distal bands of 1q. Characteristic manifestations include round face with prominent “cupid's bow” and downturned corners of the mouth, thin vermilion borders of lips, long upper lip with smooth philtrum, short and broad nose, epicanthal folds, apparently low‐set ears, micrognathia, microcephaly, abnormal hands and feet, variable cardiac, genital, and other anomalies, moderate to severe mental retardation, and growth retardation. The deletion includes 1q42 or 1q43→qter and was a de novo defect in nine of 15 cases.
Epidemiology of neural tube defects in South America
Authors: Castilla Eduardo E. , Orioli Iěda M. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe present data from the Latin American Collaborative Study of Congenital Malformations (ECLAMC) on prevalence rates and etiologic factor associations in neural tube defects. Two series of data are analyzed: the A series, including 740, 139 consecutive infants born in the 1967–1979 period suitable for secular trend analysis and case‐control study of risk factors; and the B series, including 255, 834 consecutive stillborn and liveborn infants of the 1980–1982 period suitable for prevalence rate analysis. Anencephaly was registered in 6.0/10,000 births, spina bifida aperta in 6.2/10,000 births, and cephalocele in 2.4/10,000 births. A stable secular trend was observed for the frequency of all three neural tube defect types. Spina bifida was more frequent in Chile than in the rest of South America. No differences in prevalence rates were seen between tropical and non tropical areas. Parental consanguinity and environmental prenatal factors including maternal illnesses, drug intake, and radiation exposure were found in association with anencephaly and spina bifida.
Heterozygous cystinuria and urinary lithiasis
Authors: Giugliani Roberto , Ferrari Iris , Greene Lewis J. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractCystinuria is a recessively inherited transport disorder, with at least three mutant alleles (I, II, and III) demonstrable. I/I, II/II, and III/III homozygotes and I/II, I/III, and II/III compound heterozygotes (cystinuric patients) have high urinary concentrations of cystine, lysine, arginine, and ornithine and frequently form cystine stones. +/I heterozygotes (nondetectable) are phenotypically normal, whereas +/II and +/III heterozygotes (detectable) show variable increases in urinary cystine and lysine concentration and at times increases in urinary arginine levels. The objectives of the present study were to determine the frequency of +/II heterozygotes among stone‐forming and nonstone‐forming individuals from the same region of Brazil and to evaluate the possible relationship between heterozygous cystinuria and urinary lithiasis.When urine samples from 5,150 individuals (5,000 nonstone‐forming individuals and 150 stone‐forming individuals) were screened by the qualitative cyanidenitroprusside cystine test, by thin‐layer amino acid chromatography, and by quantitative amino acid determination by ion‐exchange chromatography, 32 +/II or +/III heterozygotes (26 nonstone‐forming and six stone‐forming individuals) were detected. The frequency of detectable heterozygotes among the stone‐forming individuals (1:25) was significantly higher than that among nonstone‐forming individuals (1:104), which provides additional evidence that heterozygosity for +/II and +/III cystinuria is a risk factor in the formation of urinary stones. No significant difference was detected in urinary cystine concentration or in terms of the various characteristics of urolithiasis when stone‐forming heterozygotes were compared to nonstone‐forming heterozygotes. These data suggest that the tendency towards stone‐forming among heterozygotes is probably owing to a complex and multifactorial mechanism.
Segregation patterns and phenotypes of unbalanced offspring in a large family with (10;18) chromosome translocation
Authors: Bernstein Reneé , Pinto Maximina R. , Kromberg Jennifer , Wagner Joan , Jenkins Trefor , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe describe a large family in whom a balanced 10;18 chromosome translocaton is segregating through five generations. Six severely mentally retarded relatives and an abnormal fetus further define the phenotypic expression of dup (18q21 → qter). Other segregants detected prenatally included a fetus with deletion 18q21 → qter and two fetuses with dup(18pter → q21) owing to tertiary trisomy. One of the latter also had an extra X chromosome; this might be another example of possible nonhomologous pairing in man.
Histologic and ultrastructural studies on the mineralization process in hypophosphatasia
Authors: Ornoy Asher , Adomian Gerald E. , Rimoin David L. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractChondroosseous tissue from six infants with infantile hypophosphatasia and six control infants were studied by light, transmission, and scanning electron microscopy. Alkaline phosphatase histochemical reaction of the growth plate was studied in two infants and was greatly reduced when compared to two control infants. Hypertrophic chondrocytes were increased in number with persisting cartilage islets in the metaphysis. In five of the six cases studied, chondrocytes and intercartilagenous intercellular chondroid matrix appeared ultrastructurally normal. Matrix vesicle distribution was similar to that of control subjects, but they were associated with few mineral crystals. In two infants, the matrix vesicles were alkaline phosphatase nonreactive. In the calcifying zone of the growth plate and in the newly formed metaphyseal trabecular bone, cartilagenous calcospherites often were small and the orientation of crystals was nonradial when compared to that of control infants. The mineralization of diaphyseal bone appeared normal. It seems that matrix vesicles are present in hypophosphatasia and that the impaired mineralization of cartilage is due primarily to the deficiency of alkaline phosphatase. In spite of the lack of alkaline phosphatase, secondary mineralization of bone which is not mediated by matrix vesicles was normal.
Planning a statewide genetic screening program: Defining program functions to achieve desired outcomes
Authors: Harris Mary S. , Carriere Andree R. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWhen responsibility for administering the Genetic Screening Program in Georgia was transferred from an academic institution to state authority in 1982, the need was identified to reassess program planning. Accordingly, a cooperative effort was initiated between the Director of the Genetic Screening Program and representatives of the Centers for Disease Control to define desired program outcomes and the functions that should be performed to achieve these outcomes.This cooperative effort resulted in the development of specific and measurable outcomes for Georgia's Genetic Screening Program. These desired outcomes indicate the degree of reduction in morbidity and mortality associated with genetic diseases the Program is expected to achieve within a specified period of time. The major actions that should be taken to achieve these outcomes were also identified and delineated in sequence using flowchart format.These explicit descriptions of desired program outcomes and the functions necessary to achieve these outcomes provide the Genetic Screening Program Director with a valuable resource to use in planning program activities and assessing the extent to which the Program is successful in achieving its overall goal of reducing morbidity and mortality associated with genetic diseases.
Dermatoglyphic indices of males with the fragile X syndrome and of the female heterozygotes
Authors: Simpson Nancy E. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractIndices for males with the fragile X [fra(X)] syndrome and for the female heterozygotes have been established. The indices were based on the increased frequencies of whorls and radial loops on the third digits of affected males and heterozygous femal increased frequency of arches on the third digits of the affected males, and an excess of low ab ridge counts and abnormal palmar creases, particularly the Sydney crease, in both sexes. The indices were calculated using the logN odds ratio based on the frequencies of the above dermatoglyphics and palmar creases in 47 males with the syndrome compared to 497 male controls and 36 heterozygous females compared to 493 female controls. The indices had similar distributions in males and females. Seventy per cent of males with the syndrome and 67% of female heterozygotes had an index ≥ +0.5. Thirty‐one per cent of female heterozygotes who had both the dermatoglyphic index calculated and their chromosomes examined under appropriate conditions for the fra(X) site had an index < +0.5 and had less than 2% fragile sites (most had none). However when the two tests were considered together, only 4/35 (11%) of the heterozygotes would not have been identified using the two criteria. The data suggest that the dermatoglyphic index is a helpful adjunct test with chromosome analysis for the identification of fra(X) heterozygotes.
Oral findings in fragile X syndrome
Authors: Shellhart W. Craig , Casamassimo Paul S. , Hagerman Randi J. , Belanger Gary K. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThis study compares the oral findings in fragile X syndrome individuals to those of normal age‐matched patients. Sixteen fra(X) males (mean age 22 10/12 years) had a low caries rate (decayed, missing and filled surfaces (DMFS) = 12.3) and minimal intraoral hard or soft tissue disease. Rate of malocclusion, as determined by the first permanent molar classification of Angle, was not significantly different from that of matched subjects. Fra(X) subjects had a significantly higher occurrence of malocclusion as compared to matched subjects using crossbite and openbite as criteria. Palatal dimensions of fra(X) subjects did not differ significantly from those of the matched sample. The fra(X) males also demonstrated significantly more severe occlusal wear of their teeth than the matched sample.
Speech disturbances (cluttering) in mildly impaired males with the Martin‐Bell/fragile X syndrome
Authors: Hanson Donna M. , Jackson Alfred W. , Hagerman Randi J. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThe language characteristics of fra(X) males (n = 10) with an IQ ≥ 70 were evaluated. Language testing demon strated relatively stronger receptive vocabulary skills compared to weak auditory memory and processing skills. A characteristic speech and language disturbance, cluttering, was present in 9 of the 10 study patients. Their speech was characterized by a fast and fluctuating rate of speech, and repetitions of sounds, words or phrases. Other aspects of cluttering including attentional problems, hyperactivity, motor delays and reading difficulties are commonly seen in the fra(X) syndrome. Cluttering may be helpful in identifying the fra(X) syndrome in a male who is not retarded.
Metaphyseal dysostosis and congenital nystagmus in a male infant with the fragile X syndrome
Authors: Williams Charles A. , Cantú Eduardo S. , Frías Jaime L. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractA 14‐month‐old male with congenital nystagmus, sparse scalp hair, protuberant ears, developmental delay, and radiologic manifestations of mild metaphyseal dysostosis was coincidentally found to have the fra(X) chromosome in 67% of analyzed metaphases. This observation underscores the need for fra(X) analyses in children with developmental deficit of unknown cause.
Gonadal function in men with the Martin‐Bell (fragile‐X) syndrome
Authors: Berkovitz Gary D. , Wilson Don P. , Carpenter Nancy J. , Brown Terry R. , Migeon Claude J. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe evaluated testicular function in 15 men with the Martin‐Bell (fragile‐X) mental retardation syndrome. Macro‐orchidism was present in all subjects. Their mean serum LH and FSH levels and plasma testosterone and dihydrotestosterone levels were normal. The mean plasma levels of androstenedione, 17‐hydroxyprogesterone, and progesterone were slightly elevated above the normal range, whereas the plasma levels of dehydroepiandrosterone and dehydroepiandrosterone‐sulfate were normal. The response in the levels of plasma testosterone following a 5 day period of hCG stimulation was normal in 8 subjects and there was no abnormal accumulation of androgen precursors. The level of 5α‐reductase activity and androgen receptor binding was normal in genital skin fibroblasts derived from 3 of these patients. The response of gonadotropin secretion to GnRH stimulation was normal in the 8 men who were tested. Therefore, ourdata are consistent with the hypothesis that testicular enlargement in men with the Martin‐Bell syndrome is not mediated by hormonal factors.
Oral folic acid versus placebo in the treatment of males with the fragile X syndrome
Authors: Hagerman Randi J. , Jackson Alfred W. , Levitas Andrew , Braden Marcia , McBogg Pamela , Kemper Melinda , McGavran Loris , Berry Rebecca , Matus Irwin , Hagerman Paul J. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractA double‐blind, crossover study of a 10 mg folic acid per day (vs. placebo) treatment was carried out in 25 fra(X)males (ages 1–31 years). Each treatment period lasted 6 months. Before, during and after the study, the patients were assessed blindly with psychological, language and behavioral evaluations, and parent or caretaker reports were collected. Standardized testing did not show statistically significant changes in the group as a whole; psychological testing demonstrated a statistically significant improvement on folic acid in the prepubertal male After undercoding, caretaker or parent reports also demonstrated behavioral improvements in the prepubertal males while being treated with folic acid.
Second trimester prenatal diagnosis of the fragile X
Authors: Tommerup Niels , Aula Pertti , Gustavii Björn , Heiberg Arvid , Holmgren Gösta , von Koskull Harriet , Leisti Jaakko , Mikkelsen Margareta , Mitelman Felix , Nielsen Karen B. , Steinbach Peter , Stengel‐Rutkowski Sabine , Wahlström Jan , Zang Klaus , Zankl Merve , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThe fra (X) chromosome was detected in 5 samples of amniotic fluid cells in a series of 23 pregnancies at risk. The prenatal results were confirmed in 2 male abortuses, one with a relatively high and one with a very low frequency of expression in both amniocytes and fetal tissue. In a third male fetus with low expression in amniocytes, the fra (X) was not detected in the fetal tissues tested. In another male with low expression in amniocytes the fra (X) was not detected after birth. In one female with a low expression in amniocytes, a very high frequency (28%) was detected in cord blood after birth. Low expression of the fra(X) was found in a 4‐year‐old normally developed girl, where the prenatal results had been negative. In 4 males and 4 females the negative prenatal diagnoses were confirmed after birth. This study indicates that prenatal diagnosis of the fragile X after amniocentesis may be complicated, either due to technical problems related to the use of amniotic fluid cells, or due to genetic heterogeneity, or both. Part of this heterogeneity could be due to the existence of normal male transmitters. Also, it seems that the frequency of expression in amniocytes from female carriers can not be used for the prediction of the frequency in blood after birth.
Infantile autism and the fragile X. A swedish multicenter study
Authors: Wahlström Jan , Gillberg Christopher , Gustavson Karl‐Henrik , Holmgren Gösta , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractIn a Swedish multicenter study of 122 cases of infantile autism 16 boys (13%) were found to be fragile (X)(q27) positive. None of the 21 girls studied were fragile (X) positive.
Effects of nucleotides on expression of the folate sensitive fragile sites
Authors: Sutherland Grant R. , Baker Elizabeth , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractFurther studies on the effect of nucleotides upon expression of the folate sensitive fragile sites have confirmed that high concentrations of thymidine (300 mg/l) but not BrdU (600 mg/l) induce these fragile sites. Induction by thymidine can be supressed by addition of cytidine in a dose response manner. Studies on other nucleotides suggest that guanosine, but not adenosine or cytidine, can induce the fragile sites. The previously hypothesised model for the DNA at a fragile site as a naturally occurring polypurine/polypyrimidine sequence which becomes amplified is further developed.