bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pentalogy of Cantrell and ectopia cordis, a familial developmental field complex
Authors: Martin Rick A. , Cunniff Christopher , Erickson Lars , Jones Kenneth Lyons 
Published: June 2005

AbstractThe association of sternal fusion defects with various cardiac, diaphragmatic, and anterior body wall defects represents a developmental field complex that includes the Pentalogy of Cantrell and ectopia cordis. No familial cases have been reported previously. We present 3 consecutively born brothers with extensive diaphragmatic defects, 2 who had the Pentalogy of Cantrell. One of the 2 also had ectopia cordis.
Longitudinal changes in IQ among fragile X males: Clinical evidence of more than one mutation?
Authors: Fisch G. S. , Shapiro L. R. , Simensen R. , Schwartz C. E. , Fryns J. P. , Borghgraef M. , Curfs L. M. , Howard‐Peebles P. N. , Arinami T. , Mavrou A. 
Published: June 2005

AbstractLongitudinal changes in IQ among mentally retarded (MR) fragile X [fra(x)] males have been reported previously. While age is associated with decline in IQ, not all males are so affected. This suggests that there may be more than one subtype of affected fra(X) male. Therefore, we examined the distribution of standardized difference scores (Zdiff) in IQ to determine if subjects were from an admixture of at least 2 populations. Cluster analysis of Zdiff scores was used to partition subjects into 2 groups. Goodness‐of‐fit tests indicated that scores were more likely to come from an admixture. Discriminant functions (DF) were calculated to determine predictive validity of Zdiff scores. To eliminate the effect of skewing, a power transform was applied to Zdiff scores and DFs recomputed. Zdiff and transformed scores provided similar results. The mean and variance for one group showed no differences in test‐retest scores as would be expected from examining any population while the mean for the second group indicated significant decline in IQ nearly 4 standard errors below the first test score. These results suggest that there may be clinical evidence for 2 types of fra(X) mutation: One which causes MR but is static, and a second mutation which causes MR but is dynamic and contributes to an apparent longitudinal decline in cognitive function.
Brief screening questionnaire for determining affected state in fragile X Syndrome: A consensus recommendation
Authors: Reiss Allan L. , Cianchetti Carlo , Cohen Ira L. , Devries Bert , Hagerman Randi , Hinton Veronica , Froster Ursula , Lachiewicz Ave , Mazzocco Michele , Sobesky William , Sudhalter Vicki 
Published: June 2005

AbstractNew molecular research has provided strong evidence for different forms of the fragile X mutation. These findings suggest the need to develop a more standardized and sensitive method for determining neurobehavioral effects of the fragile X gene (s), particularly for molecular studies of patients who do not have obvious mental retardation. This report describes a brief screening questionnaire designed to increase the detection of neurobehavioral dysfunction in individuals from fragile X families who are included in new molecular studies. Improved detection of the affected state in fragile X syndrome will allow more valid clinical data to be correlated with the important molecular information currently being collected.
Mode of inheritance influences behavioral expression and molecular control of cognitive deficits in female carriers of the fragile X syndrome
Authors: Hinton V. J. , Dobkin C. S. , Halperin J. M. , Jenkins E. C. , Brown W. T. , Ding X. H. , Cohen I. L. , Rousseau F. , Miezejeski C. M. 
Published: June 2005

AbstractThe effect of mode of inheritance on expression of fragile X syndrome [fra(X)] was investigated in nonretarded female carriers. Examination included cognitive and molecular measures. A priori predictions about cognitive impairment and size of an unstable region of DNA containing a CGG repeat on the X chromosome were tested in age and education matched heterozygotes grouped according to parental inheritance.Nine carriers with a maternal fra(X) chromosome, 11 carriers with a paternal fra(X) chromosome and 15 control mothers of children with non X‐linked developmental disabilities were tested. Inheritance was established through DNA linkage analysis. Cognitive skills were assessed using the Wechsler Adult Intelligence Scale‐Revised and the Benton Visual Retention Test. Molecular status was assessed by Southern blot analysis of genomic DNA digested with Eco RI and Eag I, and probed with StB 12.3.Results supported the inheritance models' predictions. Heterozygotes who inherited the fra(X) from their fathers appeared to be a homogeneous group. They were indistinguishable from controls on cognitive measures and all had genomic insertions of <500 base pairs. In contrast, heterozygotes who inherited the fra(X) chromosome from their mothers appeared to be made up of 2 subpopulations. They were as a group deficient in measures of attention and visual memory, but not other measures, with scores of some women consistently below the other subjects. Further, they had some members with >500 base pair inserts.Thus, parental origin of the chromosome appears to influence fra(X) expression on both a behavioral and molecular level.
Cognitive profile in adult, normal intelligent female fragile X carriers
Authors: Steyaert J. , Borghgraef M. , Gaulthier C. , Fryns J. P. , Van Den Berghe H. 
Published: June 2005

AbstractHere we present the results of the study of the cognitive profile of 11 adult, normally intelligent female fragile X [fra(X)] carriers. In all individuals 3 types of testing were performed: full scale Wechsler Adult Intelligence Scale, a set of neuropsychological tests and an arithmetic achievement test.All 11 subjects showed an average to above‐average intelligence but 10 of 11 performed better on the performance than on the verbal subscale. Neuropsychological tests suggest a dysfunction of the reticulo‐thalamic axis with deficiency on tests requiring visual memory and a pronounced deficiency of attention skills combined with an impulsive way of completing tests.
Mortality in the fragile X syndrome: Preliminary data
Authors: Partington M. W. , Robinson H. , Laing S. , Turner G. 
Published: June 2005

AbstractMortality was studied among 348 males and 433 females who had or who carried the gene for the fragile X syndrome. The average age of death was about 12 years lower than in the general population for both men and women but this was likely a bias of ascertainment. The commonest causes of death were cardiovascular, cerebrovascular and malignant disease similar to those in the general population. No evidence for any specific disease subsceptibility was found in this preliminary study.
Sleep apnea in fragile X syndrome
Authors: Tirosh Emanuel , Borochowitz Zvi 
Published: June 2005

AbstractSeven subjects (age 6 to 21 years) with fragile X [fra(X)] were investigated for obstructive sleep apnea (OSA). After a structured interview, 4 of them underwent an overnight polygraphic study. The results indicate an increased risk for OSA among subjects with fra(X) (4/7). In 2 of the subjects polygraphic study indicated a severe OSA syndrome, whereas only mild and moderate severity was evident in the other two. Apnea in all 4 was associated with significant O2desaturation. Episodes of prolonged expiratory apnea were reported in 2 of the subjects and confirmed by the polygraphic study in one. A continuous positive airway pressure (C‐PAP) trial was successful in one of the two patients. It is suggested that subjects with fra(X) are at increased risk for OSA, and physicians should orientate their evaluation with this in mind.
Fra(X)(q27.2), the common fragile site, observed in only one of 760 cases studied for the fragile X syndrome
Authors: Jenkins Edmund C. , Genovese Marilyn J. , Duncan Charlotte J. , Gu Hong , Stark‐Houck Sandra L. , Lele Kusum , Li Shu‐Yun , Krawczun Michael S. 
Published: June 2005

AbstractCell cultures from 760 whole blood, amniotic fluid, chorionic villus sample, and peripheral umbilical blood sample specimens were exposed to multiple fra(X)(q27.3) induction systems (none had aphidicolin). Fifty‐three exhibited the rare fragile site, fra(X)(q27.3) or FRAXA, none of which demonstrated the common fragile site or FRAXD at band Xq27.2. Only one cell in one of the negative whole blood FUdR‐treated cultures from a mentally retarded male showed FRAXD. Therefore, it appears that FRAXD occurs very rarely in cultures treated to induce FRAXA since only one positive cell was observed in over 88,000 analyzed. It appears that very low frequencies of fra(X)(q27) can be accounted for only in part by the presence of the common fragile site, since only one of 9 cases, each with one fra(X)(q27) positive cell, exhibited FRAXD and the others were FRAXA. After confirmation of FRAXA with direct DNA testing in a large number of low frequency cases, it should be possible to rely on the detection of very low frequencies of fra(X)(q27.3), e.g., 1% with at least 2 positive cells.
Factors which contribute to cytogenetic frequency of expression in families of fragile X females
Authors: Fisch Gene S. , Fryns Jean‐Pierre 
Published: June 2005

AbstractFrequency of expression in mentally retarded (MR) fragile X (fra[X]) males has been shown to be affected by genetic factors and laboratory procedures. Among MR females, factors that contribute to cytogenetic expression have been more problematic in part due to lower frequency of expression and X‐inactivation. We examined fra(X) sisters to determine whether genetic factors affecting frequency of expression in sisters were comparable to those in brothers. Evaluations obtained from 2 data sets for a total of 66 families in which at least 2 affected brothers and/or 2 affected sisters were found cytogenetically positive were selected. Of 166 subjects chosen, 118 were male and 48 were female. Sibs were evaluated using an analysis of covariance (ANCOVA) with 2 factors (family, sex) adjusted for the covariate, age. Results indicated that interactive effects (family‐by‐sex) and main effects (family, sex, age) were significant but the interactive effect of age‐by‐sex was not. Consequently, one‐way analyses of variance (ANOVA) of the effect of family were calculated separately for brothers and sisters. Correlation coefficients between family and cytogenetic frequency was r=.84 for brothers and r=.79 for sisters. Analysis of these coefficients indicated that they were not significantly different from one another (Z=0.85, p>.40). While other factors may affect cytogenetic expression, whatever familial factors control frequency of expression among brothers appear to affect frequency of expression among sisters as well.
Dialyzed fetal Bovine serum increases cytogenetic fragile X expression
Authors: Jenkins Edmund C. , Duncan Charlotte J. , Gu Hong , Genovese Marilyn , Krawczun Michael S. 
Published: June 2005

AbstractShort‐term whole blood cultures from 9 unrelated male individuals with the fragile X [fra(X)] syndrome were exposed to 5‐fluorodeoxyuridine (FUdR). The fra(X) frequency was higher in 8 of 9 cases where the complete medium contained dialyzed fetal bovine serum (DFBS). In 3 of the cases, the fra(X) frequency nearly tripled (e.g., 12/100 to 33/100) while in 2 others, it nearly doubled (e.g., 15/100 to 29/100). When DFBS cultures from 2 other fra(X) individuals were exposed to increasing folic acid concentrations ranging from 2 to 4,000 × 10−6 M, there was virtually no change in fra(X) expression.In 6 of 9 DFBS cultures, the mitotic index decreased, and it increased in 3. Therefore, although the fra(X) frequency increased, in most DFBS cultures the mitotic index decreased. Whether the reduction in mitotic index indicates an inverse correlation between reduced mitotic index and increased fra(X) expression, at least in cultures from some individuals, will be determined by additional studies.In conclusion: (1) medium supplementation with dialyzed fetal bovine serum should be considered when using FUdR for fra(X) identification in order to avoid potentially false negative results; (2) there appears to be no direct correlation between increased mitotic index and increased fra(X) expression in whole blood cultures; (3) increased folic acid concentrations do not affect fra(X) expression when FUdR fra(X) induction is employed; therefore requesting people to refrain from taking vitamins, including folic acid, before fra(X) testing (a practice that still persists in some places) appears unnecessary.
Prenatal cytogenetic diagnosis of the fragile X chromosome: Feasibility and speed of in situ clonal method in amniotic fluid cell tissue culture
Authors: Shapiro Lawrence R. , Wilmot Patrick L. , Andree Lynn E. 
Published: June 2005

AbstractWe have had experience with over 300 amniotic fluid specimens for prenatal diagnosis for the fragile X chromosome [fra(X)], and the flask method of tissue culture has been routinely utilized requiring extended tissue culture periods of 3–4 weeks. The use of the in situ clonal method of tissue culture for routine prenatal cytogenetic diagnosis of amniotic fluid cells has shortened tissue culture time and resulted in more rapid reporting; however, it has not been widely employed for fra(X) prenatal diagnosis.The simultaneous use of both methods of tissue culture has resulted in the detection of 2 cytogenetically fra(X) positive cases in amniotic fluid, with more rapid reporting and satisfactory expression of the fra(X) with the in situ clonal method.Thus, the use of the in situ clonal method of tissue culture for fra(X) prenatal diagnosis in amniotic fluid cells is feasible, faster and can serve as a more rapid cytogenetic adjunct to the newer DNA testing methods.
Prenatal cytogenetic diagnosis of the fragile X syndrome in amniotic fluid: Calculation of accuracy
Authors: Shapiro Lawrence R. , Wilmot Patrick L. , Fisch Gene S. 
Published: June 2005

AbstractWe have completed over 350 prenatal diagnoses for the fragile X [fra (X)] syndrome using amniotic fluid, chorion villus specimen (CVS), fetal blood sampling and molecular methods. A total of 300 amniotic fluid specimens have been received for prenatal diagnosis of the fra(X) syndrome. There was a documented family history of fra(X) in 170/300 amniotic fluid cases, and 23/170 were correctly identified as cytogenetically fra(X) positive (16 male; 7 female). Three males were false‐negative, and one female was fra(X) negative but identified as a probable carrier by RFLPs. No fra(X) positive or false‐negative results were found in the absence of a fra(X) family history.Because the a priori risk for the fra(X) syndrome for each pregnancy was different and widely variable, the determination of the accuracy of the prenatal diagnosis results requires a consideration of these variables. On this basis, the calculated accuracy of prenatal cytogenetic diagnosis for the fra(X) syndrome is approximately 97%. This accuracy can be improved further with the simultaneous use of molecular methods, especially in view of recent developments.
Prenatal diagnosis of fragile X syndrome: Results from parallel molecular and cytogenetic studies
Authors: Murphy Patricia D. , Wilmot Patrick L. , Shapiro Lawrence R. 
Published: June 2005

AbstractSince 1985, we have provided coordinated DNA‐based and cytogenetic prenatal analysis for couples at risk for offspring afflicted with the fragile X [fra(X)] syndrome. To date, 40 pregnancies have been studied (22 males, 18 females). There were 5 males and 3 females identified to be at high risk by DNA but only 2 males and one female were demonstrated to be cytogenetically expressing the fra(X) prenatally. Of the other 3 males, one was a cytogenetic false negative (i.e. confirmed fra(X)+ at termination of pregnancy). The other 2 remain fra(X)‐ and are developing normally (undetected recombinants or non‐penetrat male carriers). All fetuses at low risk were carried to term and are reported to be normal.
Analysis of full fragile X mutations in fetal tissues and monozygotic twins indicate that abnormal methylation and somatic heterogeneity are established early in development
Authors: Devys D. , Biancalana V. , Rousseau F. , Boué J. , Mandel J. L. , Oberlé I. 
Published: June 2005

AbstractThe fragile X syndrome, the most common cause of inherited mental retardation, is characterized by unique genetic mechanisms, which include amplification of a CGG repeat and abnormal DNA methylation. We have proposed that 2 main types of mutations exist. Premutations do not cause mental retardation, and are characterized by an elongation of 70 to 500 bp, with little or no somatic heterogeneity and without abnormal methylation. Full mutations are associated with high risk of mental retardation, and consist of an amplification of 600 bp or more, with often extensive somatic heterogeneity, and with abnormal DNA methylation. To analyze whether the latter pattern is already established during fetal life, we have studied chorionic villi from 10 fetuses with a full mutation. In some cases we have compared them to corresponding fetal tissues. Our results indicate that somatic heterogeneity of the full mutation is established during (and possibly limited to) the very early stages of embryogenesis. This is supported by the extraordinary concordance in mutation patterns found in 2 sets of monozygotic twins (9 and 30 years old). While the methylation pattern specific of the inactive X chromosome appears rarely present on chorionic villi of normal females, the abnormal methylation characteristic of the full mutation was present in 8 of 9 male or female chorionic villi analyzed. This suggests that the methylation mechanisms responsible for establishing the inactive X chromosome pattern and the full mutation pattern are, at least in part, distinct. Our results validate the analysis of chorionic villi for direct prenatal diagnosis of the fragile X syndrome.
Molecular studies of the fragile X syndrome
Authors: Knight Samantha J. L. , Hirst Mark C. , Roche Anya , Christodoulou Zoe , Huson Susan M. , Winter Robin , Fitchett Margaret , McKinley Mark J. , Lindenbaum Richard H. , Nakahori Yutaka , Davies Kay E. 
Published: June 2005

AbstractWe have studied families segregating for the fragile X syndrome for the presence of amplification of the CGG repeat sequence adjacent to the HpaII Tiny Fragment (HTF) island in the FMR‐1 gene. We demonstrate that 138/143 fragile X positive, mentally retarded males show a characteristic smear of fragments corresponding to somatic variation in the amplification of the CGG sequence. In 7/8 normal transmitting males (NTM's), we show that there is a small amplification of sequence but no evidence for somatic variation. Defined mutated fragments in the size range found in NTM's are seen in daughters of NTM's. The daughters of these female carriers show either a defined fragment in the NTM size range, a defined larger fragment or a heterogeneous pattern of fragments. In the latter 2 cases the clinical phenotype of the females cannot easily be predicted, presumably because of variable X inactivation. In some families, the observed DNA genotype does not correlate with the phenotype; in others we demonstrate the occurrence of individuals with a mosaic DNA genotype. The implications of these data for diagnosis of the disease are discussed.
Three families with high expression of a fragile site at Xq27.3, lack of anomalies at the FMR‐1 CpG Island, and no clear phenotypic association
Authors: Oberlé I. , Boué J. , Croquette M. F. , Voelckel M. A. , Mattei M. G. , Mandel J. L. 
Published: June 2005

AbstractWe report on 3 families where the presence and segregation at high frequency of a fragile Xq27.3 site is not associated with the mutations and methylation anomalies typically seen in the fragile X [Fra(X)] syndrome. In one family, a folate insensitive fragile site was associated with Robin sequence in the propositus. In a second family a fra(X) negative mother has two fra(X) positive sons (one mentally retarded and the other newborn). The third family presents very high expression of a folate sensitive site, unlinked to mental retardation, and was described previously by Voelckel et al. [1989]. The fragile sites in these or similar families recently described must be different from the one associated with the fra(X) syndrome. Their association with a clinical phenotype or with mental retardation is certainly not consistent, and may represent an ascertainment bias. However, the relatively high frequency with which they have been found among previously diagnosed fra(X) families suggests that, at least in some cases, the association with mental impairment may be significant. In two families reported up to now, a male with high expression of such variant fra(X) site failed to transmit it to his daughter, which may reflect an imprinting effect. Previously diagnosed families should be reinvestigated before direct DNA analysis is used for prenatal or carrier diagnosis of the fra(X) syndrome.
Analysis of mutations at the fragile X locus using the DNA probe Ox1.9
Authors: Snow Karen , Doud Laurie , Hagerman Randi , Hull Claire , Hirst Mark C. , Davies Kay E. , Thibodeau Stephen L. 
Published: June 2005

AbstractIn this study, 40 families segregating for fragile X [fra (X)] syndrome were examined for the presence of a mutation within the FMR‐1 gene. Using the DNA probe Ox1.9, both carriers and affected individuals were found to contain an insertion/amplification‐type of mutation with somatic instability. Variability in the size of the mutation, which ranged from less than 0.2 kb to approximately 13 kb, was observed both between individuals (even from the same family) and within individuals, who showed a smear rather than a discrete band(s) on Southern blot analysis. Transmission of the mutation by males resulted in little change of its size, while transmission by females usually resulted in an increase in size. Correlations were observed between the size of inserted/amplified DNA and the level of chromosome fragility and the presence or absence of mental impairment. Overall, a mutation was detected in 66 of 67 (99%) clinically affected males, in 12 of 13 (92%) transmitting males and in 95 of 112 (85%) carrier females. Equivocal results were obtained in 12 (11%) of the carrier females. No mutation was detected in 58 females and 33 males predicted to be normal by linkage, or in one female and 36 normal control males. These results strongly suggest that the mutation detected by Ox1.9 is closely associated with the cytogenetic and clinical expression of fra(X) syndrome. Additionally, the use of this probe along with other probe/enzyme combinations should provide a sensitive clinical assay for the detection of carriers of fra(X) syndrome.
Concerning the role of X‐inactivation and DNA methylation in fragile X syndrome
Authors: Migeon Barbara R. 
Published: June 2005

AbstractElucidation of the role of DNA methylation in X chromosome inactivation along with recent studies of the fragile X mutation suggests that DNA methylation is likely to be a late event in the pathogenesis of the fragile X syndrome. Thus far, the evidence does not support suggestions that an impediment to X reactivation and failure to demethylate the inactive X in oocytes is responsible for silencing the fragile X. The role of DNA methylation is probably secondary to amplification of the CGG repeat to a critical size whether on active or inactive X. Further studies are needed to determine if late replication of the inactive X predisposes the locus on that chromosome to more extensive amplification.