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1. |
Sixth international workshop on the fragile X and X‐linked mental retardation |
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American Journal of Medical Genetics,
Volume 51,
Issue 4,
1994,
Page 281-293
Grant R. Sutherland,
W. Ted Brown,
Randi Hagerman,
Ed Jenkins,
Herbert Lubs,
Jean‐Louis Mandel,
David Nelson,
Giovanni Neri,
Michael W. Partington,
Robert I. Richards,
Roger Stevenson,
Gillian Turner,
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ISSN:0148-7299
DOI:10.1002/ajmg.1320510402
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1994
数据来源: WILEY
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2. |
Fragile X phenotype in a patient with a large de novo deletion in Xq27‐q28 |
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American Journal of Medical Genetics,
Volume 51,
Issue 4,
1994,
Page 294-297
Susan G. Albright,
Ave M. Lachiewicz,
Jack C. Tarleton,
Kathleen W. Rao,
Charles E. Schwartz,
Renee Richie,
Michael B. Tennison,
Arthur S. Aylsworth,
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摘要:
AbstractA 2‐year‐old boy with manifestations of the fragile X syndrome was found to have a cytogenetically visible deletion of Xq27‐q28 including deletion of FMR‐1. Molecular analysis of the patient was recently described in Tarleton et al. [1993: Hum Mol Genet 2(11): 1973–1974] and the deletion was estimated to be at least 3 megabases (Mb). His mother had 2 FMR‐1 alleles with normal numbers of CGG repeats, 20 and 32, respectively. Thus, the deletion occurred as a de novo event. The patient does not appear to have clinical or laboratory findings other than those typically associated with fragile X syndrome, suggesting that the deletion does not remove other contiguous genes. This report describes the phenotype of the patient, including psychological studies. © 1994 Wil
ISSN:0148-7299
DOI:10.1002/ajmg.1320510403
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1994
数据来源: WILEY
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3. |
High functioning fragile X males: Demonstration of an unmethylated fully expanded FMR‐1 mutation associated with protein expression |
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American Journal of Medical Genetics,
Volume 51,
Issue 4,
1994,
Page 298-308
Randi J. Hagerman,
Claire E. Hull,
John F. Safanda,
Isabelle Carpenter,
Louise W. Staley,
Rebecca A. O'Connor,
Charlotte Seydel,
Michele M. M. Mazzocco,
Karen Snow,
Stephen N. Thibodeau,
Derek Kuhl,
David L. Nelson,
C. Thomas Caskey,
Annette K. Taylor,
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摘要:
AbstractFragile X (fra(X)) males with a standardized IQ score of 70 or higher represent a high functioning (HF) or nonretarded fra(X) male group. This group, which does not include nonpenetrant males, has received little research attention to date. Of 221 fra(X) males who had been evaluated through The Children's Hospital in Denver since 1981 and had completed cognitive or developmental testing, 29 (13%) were high functioning by the above definition. We found that HF males on the whole had a lower cytogenetic score and were younger than retarded fra(X) males, but there was no difference between these two groups in the number of typical fra(X) physical manifestations present. FMR‐1 DNA testing was performed on 134 fra(X) males and methylation status was determined for 51 of these. A greater percentage of HF males had a mosaic pattern or an incompletely methylated full mutation than did retarded males. A unique DNA pattern, an unmethylated fully expanded mutation, was discovered in 3 of the highest functioning fra(X) males. Protein studies performed on 2 of these males demonstrated the presence of FMR‐1 protein, albeit at lower levels than normal. FMR‐1 protein was not present in retarded fra(X) males. Significant FMR‐1 protein expression may be responsible for higher cognitive functioning in the 2 males with unmethylated fully expanded mutations compared to retarded fra(X) males. © 1994 Wiley
ISSN:0148-7299
DOI:10.1002/ajmg.1320510404
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1994
数据来源: WILEY
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4. |
No apparent involvement of the FMR1 gene in five patients with phenotypic manifestations of the fragile X syndrome |
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American Journal of Medical Genetics,
Volume 51,
Issue 4,
1994,
Page 309-314
Pietro Chiurazzi,
Esther de Graaff,
Jessica Ng,
Annemieke J. M. H. Verkerk,
Sloan Wolfson,
Gene S. Fisch,
Libor Kozak,
Giovanni Neri,
Ben A. Oostra,
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摘要:
AbstractMost fragile X patients have a significant increase in the number of CGG repeats in the FMR1 gene. Two patients were described with a deletion and one patient with a point mutation in the FMR1 gene. We describe 5 patients with a fragile X or Martin‐Bell phenotype. Two brothers were discordant for the region containing the FMR1 gene; if there is a common cause for the mental retardation this is not located in the FMR1 gene. In the other 3 patients the expression of the FMR1 gene was found to be normal and no abnormalities were noted in the FMR1 mRNA. No amplification was found in the GCC repeat which is associated with the fragile site FRAXE. We conclude that the Martin‐Bell phenotype can also be caused by mutations outside the FMRl gene. © 1994 Wiley‐Lis
ISSN:0148-7299
DOI:10.1002/ajmg.1320510405
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1994
数据来源: WILEY
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5. |
Molecular genetic screening in cytogenetically normal mentally retarded males with manifestations of fragile X syndrome |
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American Journal of Medical Genetics,
Volume 51,
Issue 4,
1994,
Page 315-316
Merlin G. Butler,
Riccardo Pratesi,
Cindy L. Vnencak‐Jones,
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ISSN:0148-7299
DOI:10.1002/ajmg.1320510406
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1994
数据来源: WILEY
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6. |
Molecular‐neurobehavioral associations in females with the fragile X full mutation |
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American Journal of Medical Genetics,
Volume 51,
Issue 4,
1994,
Page 317-327
Michael T. Abrams,
Allan L. Reiss,
Lisa S. Freund,
Thomas L. Baumgardner,
Gary A. Chase,
Martha B. Denckla,
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摘要:
AbstractIn this study, young females with the fragile X [fra(X)] full mutation (fM) were assessed using quantitative measures of mutation amplification size (Amp) as well as the ratio of active normal X chromosome to total normal X chromosome (activation ratio‐AR). Neurobehavioral assessments of females with the fM were performed and included specific and general measures of cognitive and behavioral/developmental functioning. To investigate molecular‐behavioral associations, Amp and AR were used as independent variables, while cognitive and behavioral scores were used as dependent variables. Significant correlations were observed between both molecular variables (Amp and AR) and measures of cognitive functioning, with AR showing the most consistent and robust correlations. As AR increased, overall IQ and specific subtest and area scores from the cognitive tests increased. Conversely, as Amp increased, the overall IQ and specific subtest and area cognitive scores decreased. No significant associations were observed between AR or Amp and measures of behavior or development. The molecular‐cognitive associations were generally consistent with the cognitive profile previously described in studies comparing females with fra(X) to age‐matched controls. Amp and AR were not associated with one another, nor were they associated with the same cluster of cognitive measures. Though this report does not conclusively show that AR and Amp can be used to clinically assess the risk of a female with the fM for cognitive disability, the evidence presented does suggest that these molecular variables, especially AR, reflect important underlying genetic factors contributing to the fra(X) phenotype. © 1994 Wiley
ISSN:0148-7299
DOI:10.1002/ajmg.1320510407
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1994
数据来源: WILEY
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7. |
Modeling methylation and IQ scores in fragile X females and mosaic males |
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American Journal of Medical Genetics,
Volume 51,
Issue 4,
1994,
Page 328-338
Karen Kolehmainen,
Yasha Karant,
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摘要:
AbstractBoth fragile X females and mosaic males carry a methylated FMR1 allele in some cells and an unmethylated allele in other cells. Due to FMR1 protein produced in cells with an unmethylated allele, these individuals are expected to display a less severe cognitive phenotype than non‐mosaic affected males. A larger range in cognitive abilities is expected for these individuals due to individual variation in X‐inactivation or mosaicism ratios. These cognitive effects are well documented for females and have been suggested for mosaic males. Data on fragile X females suggest an approximately linear decrease in mean IQ score as a function of the fraction of cells with the mutation carried on the active X chromosome. Analysis of these data suggests that threshold effects in the relationship between IQ score and X‐inactivation ratios are negligible, and that X‐inactivation occurs randomly (with no preferential inactivation of either X chromosome) at a stage when the embryo consists of approximately 5 cells. A similar analysis of future data on mosaic males could yield estimates of the probability that a given cell will carry a methylated FMR1 allele and of the number of embryonic cells at the time that mosaicism is established. Distributions of IQ scores among a population of heterozygotes or mosaic males are predicted for several values of these parameters. These distributions include random contributions to IQ scores due to non‐fragile‐X‐related effects, as well as X‐inactivation or mosaicism ratios that vary from one individual to another. © 1994
ISSN:0148-7299
DOI:10.1002/ajmg.1320510408
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1994
数据来源: WILEY
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8. |
Reliability of diagnostic assessment of normal and premutation status in the fragile X syndrome using DNA testing |
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American Journal of Medical Genetics,
Volume 51,
Issue 4,
1994,
Page 339-345
Gene S. Fisch,
David L. Nelson,
Karen Snow,
Stephen N. Thibodeau,
Maryse Chalifoux,
Jeanette J. A. Holden,
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摘要:
AbstractUntil recently, fragile X [fra(X)] syndrome was diagnosed by cytogenetic techniques and/or linkage analysis. Investigation of the mutation at the molecular level has shown that amplification of a polymorphic trinucleotide repeat (CGG) is diagnostic of this syndrome. Fu et al. [1991]observed that between 6–54 copies of the repeat were associated with alleles found in the general population, whereas 50–200 copies were associated with the premutation. In general, differences in copy number between the normal and premutated states are sufficiently large so that the probability of misclassification is, for all practical purposes. zero. However, there is a grey area in which members from both populations overlap. The purpose of our study was to determine the probability of misclassifying an individual from either the general or premutation population. DNA obtained from the general population and transmitting fra(X) females were analyzed from 3 centers in North America: Houston, Texas; Rochester, Minnesota; and Kingston, Ontario. The distribution of normal alleles from Houston was not significantly different from those obtained from Rochester. Therefore, these 2 samples were combined and the pooled distribution of normal alleles was compared with the pooled distribution of premutations. Results indicated that if 50 repeats were used as the cutoff criterion, sensitivity is 100%, specificity is 99.6%, and the probability that an individual has the fra(X) premutation given that the number of repeats is greater than 50 is 95%. Other cutoff criteria (45, 55, 60, 65) employed produced like findings, although 55 repeats appears to be a marginally superior criterion to 50. An independent sample from Kingston was used to verify the original assessments. Results indicated no significant differences when the pooled Houston/Rochester distribution was compared with the distribution of repeats found in the general population from Kingston. Our findings indicate that family studies should be done to establish stability/instability of alleles when more than 55 repeats are found in the proband. © 1994 Wiley‐Lis
ISSN:0148-7299
DOI:10.1002/ajmg.1320510409
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1994
数据来源: WILEY
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9. |
Is fragile X syndrome a pervasive developmental disability? Cognitive ability and adaptive behavior in males with the full mutation |
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American Journal of Medical Genetics,
Volume 51,
Issue 4,
1994,
Page 346-352
Gene S. Fisch,
Jeanette J. A. Holden,
Richard Simensen,
Nancy Carpenter,
Patricia N. Howard‐Peebles,
Anne Maddalena,
Alice Sandgrund,
Jean‐Robert Jacques,
Barbara McGann,
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摘要:
AbstractIn addition to mental retardation (MR), fragile X [fra(X)] syndrome has been associated with various psychopathologies, although it appears that the link is secondary to MR. It has been proposed that individuals with the full mutation be classified as a subcategory of pervasive developmental disorders (PDD). If fra(X) males are to be categorized as PDD, how do they compare with other types of developmental disabilities? We examined 27 fra(X) males aged 3–14 years, from 4 sites in North America. Measures of cognitive abilities were obtained from the Stanford‐Binet Fourth Edition (SBFE), while levels of adaptive behavior were evaluated using the Vineland Adaptive Behavior Scales (VABS). Control subjects were sex‐, age‐, and IQ matched children and adolescents ascertained from the Developmental Evaluation Clinic (DEC) at Kings County Hospital. At the DEC, control subjects were diagnosed as either MR (n=43) or autistic disorder (AD; n=22). To compare subjects' adaptive behavior (SQ) with their cognitive abilities (IQ), a ratio of {(SQ/IQ)x100} was computed. Results graphed as cumulative distribution functions (cdf) revealed that the cdf for AD males, who by definition are socially impaired, was positioned to the left of the cdf for MR controls, as expected. Mean ratio for AD males (70) was lower than for MR males (84). On the other hand, the cdf for fra(X) males was positioned far to the right of either AD or MR controls (mean ratio = 125). Statistical tests showed that SQ of fra(X) males was significantly higher than controls. Moreover, in 23/26 (88%) of the fra(X) males tested, SQ was greater than IQ, indicating that adaptive behavior was not as impaired as cognitive abilities. Our results have consequences for the clinical evaluation of fra(X). In particular, fra(X) individuals may appear to function at higher cognitive levels than may be the case. We suggest that, while fra(X) may produce mild to profound developmental delay, it should not be included as a separate subtype of developmental disorder. © 1994 Wiley
ISSN:0148-7299
DOI:10.1002/ajmg.1320510410
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1994
数据来源: WILEY
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10. |
Longitudinal changes in IQ among fragile X females: A preliminary multicenter analysis |
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American Journal of Medical Genetics,
Volume 51,
Issue 4,
1994,
Page 353-357
Gene S. Fisch,
Richard Simensen,
Tadao Arinami,
Martine Borghgraef,
Jean‐Pierre Fryns,
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摘要:
AbstractLongitudinal declines in IQ among fragile X [fra(X)] males have been reported previously by several investigators. Remarkably little is known about longitudinal changes in IQ scores among fra(X) females. Previously, one cross‐sectional study showed a significant negative correlation between age and IQ scores. However, a recent investigation of girls with fra(X) syndrome noted longitudinal increases in IQ scores in 8 of 11 individuals. Therefore, the purpose of this preliminary multicenter study was to determine: (1) the characteristics of longitudinal changes in IQ among fra(X) females; and (2) whether these changes were comparable to those which have been observed among fra(X) males. IQ test and retest scores for 11 fra(X) females were obtained from 3 centers: Greenwood, South Carolina; Ibaraki, Japan; and Leuven, Belgium. To ensure high reliability, only test‐retest scores from the Wechsler and Stanford‐Binet tests were used. Age of subjects at initial testing ranged from 5 to 35 years. Mean intertest interval was 4.5 years. In contrast to a report of longitudinal increases, we found 9/11 (82%) subjects demonstrated decreases in IQ scores. Mean decline was 9 points. Females over 18 years of age showed little or no change in IQ scores. Decreases in scores appeared to be related to initial IQ score. Females in the earlier longitudinal report were higher functioning than those in our study, which may account for the observed difference in direction of change; or, change in IQ score may be related to size of the fra(X) mutation. These preliminary findings are consistent with our earlier multicenter study of fra(X) males and suggest that while cognitive deficits are greater initially among males than females, longitudinal changes in IQ scores are comparable. © 1994 Wiley‐L
ISSN:0148-7299
DOI:10.1002/ajmg.1320510411
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1994
数据来源: WILEY
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