bluuebunny/crossref_metadata_2025_split huggingface dataset:
Folic acid treatment in males and females with fragile‐(X)‐syndrome
Authors: Froster‐Iskenius U. , Bödeker K. , Oepen T. , Matthes R. , Piper U. , Schwinger E. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractTen males with the fragile X (fra(X)) syndrome were treated with folic acid (10 mg/day) for 4 months in a double‐blind design study. To eight heterozygotes with mental impairment and fra(X), folic acid was given for 4 months (10 mg/day) in an effortto study possible beneficial effects of folic acid. Psychological and cytogenetic testing were carried out during the trial. There was no improvement in concentration, fine motor co‐ordination, or comprehension in the adult male and female patients of the study. One patient showed improvement under a control medications. In the females, improvement was seen only in the youngest patient, a 5‐year‐old girl. Folate treatment does not seem to be effective in fra(X) adults, but may have some effect in children of both sexes with the disorder.Cytogenetic studies using peripheral lymphocytes showed that the fra(X) frequency decreased significantly (t = 0.00856; 1% level) only in cells cultured in a folic acidfree medium but not in cells cultured in a medium with added antifolate (methotraxate). This shows a “contamination effect” of folate‐free culture medium after oral folic acid treatment of these patients. The decrease of fra(X) involves primarily the early‐replicating X when culturing with folic acid‐free medium. A synergistic suppression effect of “external folate” and BrdU is the most likely explanation of this phenomenon.
Assessment of behavior change in a fragile‐X syndrome male treated with folic acid
Authors: Wells Thomas E. , Madison Lynda S. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThe effects of folic acid treatment were assessed in a 7‐year‐old boy with Fragile‐X (fra(X)) syndrome utilizing a within‐subject experimental design. Dependent variables consisted of classroom behavior, activity level/impulsiveness, and attentiveness. While improvements in all dependent variables were observed during folic acid treatment in comparison to initial baseline/placebo conditions, these changes were maintained in a final return to the placebo condition. These results do not support unequivocally the effectiveness of folic acid treatment. Folic acid treatment may have facilitated behavior changes that were then maintained by natural contingencies in the child's environment.
Prenatal diagnosis of the fra(X) syndrome
Authors: Shapiro Lawrence R. , Wilmot Patrick L. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThe fra(X) syndrome is one of the most common causes of mental retardation, and validation of the reliability and feasibility of making the prenatal diagnosis of this disorder is important for genetic counseling and prevention. We have received a total of 74 amniotic fluid specimens for prenatal diagnosis of fra(X) from worldwide sources. Results, were obtained on 68 specimens of which 43 had a documented family history of the fra(X) syndrome. Of the 43 specimens, 23 were male and 4 were prenatally diagnosed as being affected. On the basis of the results, several conclusions follow: (1.) At least 3 different tissue culture methods should be utilized. (2.) At least 150 cells should be scored, preferably 50 from each of 3 different tissue culture methods or 100 from each method if less than 3 methods are used. (3.) While the test‐appears to be reliable, it should still be considered to be experimental until larger numbers are obtained with completed follow‐up of cases.
Fragile X expression increased by low cell‐culture density
Authors: Krawczun Michael S. , Lele Kusum P. , Jenkins Edmund C. , Brown W. Ted , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThe effect of cell density on expression of fra(X) was studied. A. lymphoblast cell line from one fra(X) individual and whole blood from another individual was tested at various cell densities using RPMI‐1640 with FudR (0.1 μM) 24 hrs before harvest. Densities from 0.25×105 to 2×106 cells/Ml were tested. Chromosomes were G‐banded and analyuzed for fra(X) frequency. Increased density caused fra(X) frequency to decline in lymphoblasts and whole blood. In the established line low density fra(X) frequency was 51.2% and decreased to 6.5% at the high density. In blood fra(X) frequency was 34.7% at low density and decreased to 18% fra(X) in high density. We suspect that of the FUdR effect may explain the results. Our results suggest that to maximize fra(X) frequency, clutures should be inititated at low density. This may be important in analysis female carriers, and obligate nonpenetrant males.
Fragile X chromosome frequency is consistent temporally and within replicate cultures
Authors: Jenkins Edmund C. , Kastin Bruce R. , Krawczun Michael S. , Lele Kusum P. , Silverman Wayne P. , Brown W. Ted , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractFragile X frequencies differ widely between different fra(X)‐positive individuals. The basis for this variation is unknown, but may reflect genetic differences or unknown environmental factors. To determine more fully the individual and familial variation in fra(X) frequencies, we studied 15 individuals. The present study showed that fra(X) frequency, with few exceptions, was consistent for the same individual both over time and within replicate cultures. This confirms previous observations by others on the consistency of fra(X) expression by others, and indicates the extent of expected variability within replicate cultures. Consideration of this variability should enable improved fra(X) identification.
The fragile X in cattle
Authors: Uchida Irene A. , Freeman Viola C. P. , Basrur Parvathi K. , Opitz John M. 
Published: June 2005

AbstractIn search of an animal model for the human fragile X syndrome, the chromosomes of Holstein cows were examined. This breed was chosen because of previous studies on the baldy calf syndrome. An achromatic gap was observed at a specific site on the X chromosome closer to the centromere than that identified in humans. This unstained gap was found in 3%–4% of cells of the following four animals: an affected calf, her sister, their mother, and an unrelated Holstein cow. The bovine fragile X may not be analogous to the human fragile X but its location may be important as a genetic marker in linkage studies involving the loci for hypoxanthine phosphoribosyltransferase (HPRT) and glucose‐6‐phosphate dehydrogenase (G‐6‐PD).
Prevalence of the fragile‐X syndrome in mentally retarded boys in a Swedish county
Authors: Gustavson Karl‐Henrik , K:son Hans Blomquist , Holmgren Gösta , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractIn an etiological study of an unselected series of mentally retarded children (IQ < 70) born 1959‐1970 in a northern Swedish county, 12 of 205 boys (5.9%) were found to have a fragile site on the distal end of the C‐chromosome (fra(X)(q27)). The incidence of the fra(X) syndrome was calculated to be 1:1500 boys in this county. If this is true for the whole of Sweden, 30–40 new cases of the fra(X) syndrome should be born yearly in Sweden. This must be considered a minimum figure, since a certain proportion of individuals with fra(X) are not observed in groups of mentally retarded patients.Next to trisomy 21, the fragile X syndrome is the most common specific cause of mental retardation among mentally retarded boys in Sweden.
An assessment of the use of flanking DNA markers for fra(X) syndrome carrier detection and prenatal diagnosis
Authors: Forster‐Gibson Cynthia J. , Mulligan Lois M. , Simpson Nancy E. , White Bradley N. , Holden Jeanette J. A. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractOne hundred and three individuals in ll unrelated families with the fragile‐X [fra(X)] syndrome were tested for polymorphisms identified bhy probes flanking the fra(X) site at Xq27.3 Two probes distal and 2 proximal to the fra(X) site were used. Thirteen known female carriers were analyzed retrospectively. DNA markers gave probabilities of carrying the mutation of 99% in 1 female, 89% in 8 females, and 10–55% in the other 4 females. We also estimated the probability of having inherited the mutation for 16 individuals of unknown fra(X) status using DNA markers and corrections for imcomplete penetrance. the DNA marker test gave risks for females of 1–6% (7 females), 15% (1 female), and 97% (1 female). In males the risks were 1–3% (6 males) and 91% (1 male). In 3 families, DNA marker data were used to calculate probabilities of ≥98.5% that transmission of the fra(X) mutation had occurred through normal males. In the retrospective studies, only 1 of 7 retarded males could have been diagnosed prenatally as having the fra(X) mutation with a probability of 99% DNA maker analysis was uninformative in 5 of these males. When fra(X) carrier status cannot be established by chromosome analysis, DNA maker studies provide an alternative test that can be used to calculate individual risks more precisely. However, linkage analysis of the probe loci in these 11 families suggests that the recombination frequency between the fra(X)locus and the factor IX gene (F9) and DXS52 may be greater than previously suggested. Until the true recombination frequencies are established and the question of heterogeneity among families is fully analyzed, caution in using DNA markers as a predictive is advised.
Speculation on the role of transposable elements in human genetic disease with particular attention to achondroplasia and the fragile X syndrome
Authors: Hoegerman Stanton F. , Rary Jack M. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe suggest that mutations for fragile X‐positive Martin‐Bell syndrome, and prehaps also for achondroplasia, may result from the insertion of transposable elements (TE's). Loss of genetic function could result from either the insertion of TE's within or adjacent to a normal chromosmal gene or, in the case of fragile X, from the loss of genes distal to the site of TE insertion following subsequent TE excision without ligation of the resulting discontinuity.The phenotypically and often cytogenetically normal transmitting males in fragile X peidgress are interpreted not as “nonpenetrant” transmitters of a fully formed fragile X but rather as transmitters of some or all of the factors necessary for necessary for TE insertion at Xq27. We consider it likely that such insertion frequently first occurs, both in some and especially in the germline, in their daughters.Our models predict that father to son transmission of causative factors would be a common occurrence in fragile X pedigrees. The absence of documented father to son transmission either points to a flaw in the models or reflects systematic bias in the collection of pedigree information.
Recombination and amplification of pyrimidine‐rich sequences may be responsible for initiation and progression of the Xq27 fragile site: An hypothesis
Authors: Nussbaum Robert L. , Airhart Susan D. , Ledbetter David H. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractHypothesis: A pyrimidine‐rich sequence (PRS) of DNA is present as a normal sequence in the q27 band of the human X chromosome. Under conditions of pyrimidine nucleotide triphosphate deprivation during S phase, deoxyuridine monophosphate is misincorporated and has to be excised during G2 by DNA mechanisms. When a simple PRS is present on both homologous X chromosomes during oogenesis, PRS may undergo amplification through non‐homologous crossing‐over ot produced the initial lesion of the fragile (X). Carriers of such initial lesions will be unaffected transmitting females or males. When an X chromosome bearing such an initial lesion is itself paired with a homologous X carrying a simple PRS during oogenesis, a much higher rate of non‐homologous crossing‐over may occur resulting in progression to an even longer stretch of pyrimidine rich DNA in this region; the increased length of PRS through amplification makes the region too long to be repaired during G2 and allows it to be seen as a fragile site in metaphase chromosome preparations. Furthermore, this amplified lesion may interfere with transcription of one or more genes in this region and produce the phenotype of the Martin‐Bell syndrome.
Univariate and bivariate analyses of cholesterol and triglyceride levels in pedigrees
Authors: Boehnke Michael , Moll Patricia P. , Lange Kenneth , Weidman William H. , Kottke Bruce A. 
Published: June 2005

AbstractA multivariate normal model for pedigree analysis is applied to fasting total serum cholesterol and total serum triglyceride measurements on 771 individuals in 95 pedigrees from Rochester, MN. Univariate and bivariate analyses are carried out to determine to what extent the aggregation and coaggregation in families of these two traits may be attributed to shared genetic and environmental factors. Pedigrees were ascertained through a sample of schoolchildren enriched for those with serum cholesterol levels in the highest and lowest deciles of their age‐ and sex‐specific distributions. Ascertainment is corrected for by conditioning the likelihood on the trait values of the probands.Univariate results confirm the findings of previous studies indicating that familial aggregation of serum cholesterol and triglyceride levels is due both to shared genes and to shared environmental factors. Results of the bivariate analyses suggest that the coaggregation of cholesterol and triglyceride levels in these families is strongly influenced by both shared genes (pleiotropy) and shared environmental factors. These findings are consistent with our understanding of lipid metabolism and of specific environmental factors known to influence both traits.
Clinical and cytogenetic survey of 39 individuals with Prader‐Labhart‐Willi syndrome
Authors: Butler Merlin G. , Meaney F. John , Palmer Catherine G. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractIn a clinical and cytogenetic survey of 39 individuals with Prader‐Labhart‐Willi syndrome (PLWS) (23 males and 16 females ranging in age from 2 weeks to 39 years), an interstitial deletion of chromosome 15 (breakpoints q11 and q13) was identified in21 cases and apparently normal chromosomes in the remainder. Studies of parental chromosome 15 variants showed that the del[15q] was paternal in origin, although chromosomes of both parents were normal. All chromosome deletions were de novo events. Possible causes for the chromosome deletion and the role of chromosome rearrangements in individuals with PLWS are discussed. Clinical characteristics of the, deletion and nondeletion groups were recorded and compared with 124 individuals reported in the literature. Individuals with the chromosome deletion were found to have lighter hair, eye, and skin color, greater sun sensitivity, and higher intelligence scores than individuals with normal chromosomes. Correlation studies of metacarpophalangeal pattern profile variables and dermatoglyphic findings indicate apparent homogeneity of the deletion group and heterogeneity of individuals with PLWS and normal chromosomes.
Trisomy 14 mosaicism in a liveborn male: Clinical Report and review of the literature
Authors: Kaplan Lawrence C. , Wayne Alan , Crowell Stephen , Latt Samuel A. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe present the history and results of chromosome analysis of a liveborn male with mosaic trisomy 14 who was initially evaluated for a congenital heart defect. His chromosome complement was 46,XY/47,XY, + 14. The phenotype of the patient is similar in many respects to that of females previously reported with mosaic trisomy 14, whereas the patient's micropenis and cryptorchidism are consistent with findings in males with dup(14q).
Diagnosis of chromosome 3 duplication q23→qter, deletion p25→pter in a patient with the C (trigonocephaly) syndrome
Authors: Preus Marilyn , Vekemans Michel , Kaplan Paige , Reynolds James F. 
Published: June 2005

AbstractThe cells of a deceased patient previously reported to have the C (trigonocephaly) syndrome were reinvestigated because his phenotype resembled that of a patient with a duplication‐deficiency of chromosome 3. This diagnosis was confirmed using fibroblasts grown from frozen cells, and his mother was shown to carry an inversion of chromosome 3 in her peripheral blood leukocytes.His findings are compared to those of another patient with the C trigonocephaly syndrome with normal chromosomes and to others from the literature. At least one other patient from the literature has a phenotype compatible with “3q duplication syndrome”.
Chromosome deletion 1q42‐43
Authors: Watson Michael S. , Gargus J. Jay , Blakemore Karin J. , Katz Sanford N. , Breg W. Roy 
Published: June 2005

AbstractWe report on a newborn male and a female of 3 years 9 months with de novo 1q42 or 43‐qter deletions. These cases are compared with ten other reported cases.
Routine amniotic fluid alphafetoprotein assay: Experience with 40,000 pregnancies
Authors: Crandall Barbara F. , Matsumoto Myles , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractOf 40,000 initial amniotic fluid samples, 0.7% had an alphafetoprotein (AFP) level ⩾ +3 standard deviations above the mean. The risk of an open neural tube defect (NTD) or other serious fetal abnormality was 61% when AFP levels measured ⩾ +3 and 87% for levels ⩾ +5 standard deviations. If the acetylcholinesterase (AChE) was positive, this risk was 84% and 95% for AFP levels of ⩾ +3 and ⩾ +5 SD, respectively, and 29% and 62% for the same levels if the AChE was negative. If the second amniocentesis AFP was also ⩾ +3, the risk of an abnormality was 96%. In this series, there were 93 open neural tube defects, and all were identified. The true false‐positive rate was 1 per 13,000 of the cases screened. The recurrence risk for an NTD was 1.8%, and the incidence of NTDs in women having amniocentesis only for maternal age was 1.5 per 1,000.
The genetics of quantifiable homeostasis: I. The general issues
Authors: Murphy Edmond A. , Trojak Joseph L. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractSome fundamental issues in developing the quantitative genetics of heritable traits are addressed. Such a trait must be capable of being represented as a quantity. Choice of the metric can be satisfactorily made only in the light of some insight into the nature of the trait and what its revealing characteristics may be. This insight is likely to change as more is known about the process, so the form and detail of the analysis is not static but perhaps continually evolving. Much has been made out of sample means and, at a more sophisticated level, Galton‐Fisher theory (the analysis of the first two moments of multivariate Gaussian variates). However, at least some processes seriously violate the assumptions underlying that theory. One such group comprises traits in which the means are unvarying and the genetic message lies in other aspects of the distribution; in these circumstances the standard summary statistics such as heritability, regression, and correlation may be totally uninformative, distracting, or even misleading. This paradox is illustrated by reference to homeostasis, where the Mendelian component lies, not in the mean, but in the degree of laxity of control. Since estimating higher moments is notoriously imprecise, the suggested remedy is the familiar and commonsense one of exploring the genetics of the intermediate states and underlying mechanisms and not only that of the resultant (“bottom‐line”) phenotype. In our chosen problem, the task of relating the outcome to the basic mechanism of inheritance calls for a detailed understanding of the homeostasis involved.
Ring chromosome 18 in a mother and son
Authors: Donlan Michael A. , Dolan Cynthia R. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractInheritance of ring chromosomes is reported infrequently. We report on a mother and her son both with a ring 18 chromosome, and describe the associated manifestations. The son had microcephaly, ptosis, short stature, and mental retardation; the mother was mentally retarded and had a similar facial appearance.
A patient with dup(10p)del(8q) and pendred syndrome
Authors: van Wouwe J. P. , Wijnands M. C. , Mourad‐Baars P. E. C. , Geraedts J. P. M. , Beverstock G. C. , van de Kamp J. J. P. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe report on a severely retarded girl with multiple congenital anomalies. Chromosome studies showed a der (8) chromosome with dup(10p) and deficiency for a small distal segment of 8q. Her father proved to be carrier of a de novo balanced translocation between chromosome 8q and 10p. At 1 year the patient was also found to have the Pendred syndrome, an autosomal recessive defect in thyroid organification. The concurrence of chromosome anomalies and single gene disorders might not be too rare, but can be easily overlooked. Yet there are important consequences for genetic counseling. Moreover, recognition of these concurrences may help gene mapping.
A bayesian method for the estimation of penetrance: Application to mandibulofacial and frontonasal dysostoses
Authors: Rogatko André , Pereira Carlos A. B. , Frota‐Pessoa Oswaldo , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe describe a Bayesian method of estimating penetrance from genealogical data. It consists of calculating the likelihood of the data alone to make inferences about penetrance without sample space considerations. The method is applied to mandibulofacial dysostosis giving a penetrance of 0.908 with 0.95 credible interval of [0.809; 0.972] and to frontonasal dysostosis giving a penetrance of 0.670 with 0.95 credible interval of [0.457; 0.851].
Suicide and attempted suicide in Huntington disease: Implications for preclinical testing of persons at risk
Authors: Farrer Lindsay A. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractSuicide behavior in Huntington disease (HD) was assessed by examining the proportion of deaths attributed to suicide among 452 deceased individuals with HD and the number and pattern of attempted suicides among a total population of 831 HD patients from the National Huntington Disease Research Roster. It was found that 5.7% of deaths among affected persons resulted from suicide and 27.6% of patients attempted suicide at least once. Comparison of this group with the general population indicated that the proportion of deaths due to suicide among persons with HD is almost four times greater than the corresponding proportion for the U.S. Caucasian population. Age at onset of HD was not significantly different between HD suicide and non‐suicide patients, although suicide occurred more frequently in the early to middle stages of the illness. The ''success'' rate among HD suicide attempters did not differ from the general population rates in several western European countries. The relatively high suicide and attempted suicide rates in HD indicate that thorough psychological testing of at‐risk persons and extensive patient support systems must be integral components of a program to identify HD gene carriers using a genetic marker.
De novo partial duplication of 17p [dup(17)(p12→p11.2)]: Clinical report
Authors: Magenis R. Ellen , Brown Michael G. , Allen Leland , Reiss Jacob , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractDuplication of band p11.2 and a small proximal portion of band p12 of chromosome 17 was noted in an infant with unusual facial appearance and left calcaneovalgus deformity. Developmental delay was documented over time. Only one other similar case has been found in the literature, but deletion of the same region is known in nine recently described cases [Smith et al, 1986]. This suggests that abnormalities of this small region of 17p are relatively common and only recently detectable with modern high‐resolution techniques.