摘要:

AbstractNeurocognitive deficits among fragile X individuals have been reported for both high and low functioning individuals. Recent findings from our research suggest a specific neurocognitive phenotype among fragile X women that is characterized by deficits on tests of frontal lobe functioning. In this paper, we examine in more detail the performance of 10 cytogenetically expressing women and 10 control women on 2 problem solving measures considered sensitive to frontal lobe functions: the Contingency Naming Test and the Tower of Hanoi. The results pertaining to each test suggest that fragile X women, relative to control women, are less able to solve a problem when the difficulty of the problem is increased by requiring simultaneous consideration of additional information. These findings have important implications for remediation strategies designed for affected fragile X individuals.

ISSN:0148-7299    

DOI:10.1002/ajmg.1320430112

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

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 of500 base pair inserts.Thus, parental origin of the chromosome appears to influence fra(X) expression on both a behavioral and molecular le

ISSN:0148-7299    

DOI:10.1002/ajmg.1320430113

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe prenatal detection of a positive fragile X [fra(X)] female raises difficult counseling issues. In order to address questions regarding the long term outlook, we have conducted follow‐up studies on 4 fra(X) positive females which were carried to term. Three were prenatally detected, and one was a false negative. The subjects were between 3 and 7 years old when follow‐up investigation of mental status was conducted. The first case age, 6 and 9/12 years, had an IQ of 106. On measures of achievement she had some difficulty with arithmetic. The second and third cases were clearly affected. They were judged to be mildly to moderately mentally retarded. The fourth case was borderline normal.The prenatal amniocentesis cytogenetic frequencies had a mean of 3.74% (range 0 ‐ 8.5%). On postnatal follow‐up testing of blood, the mean cytogenetic frequency increased to 31.75% (range 24 ‐ 47%), an 8.5 fold increase.Follow‐up DNA samples from 3 of the 4 subjects were analyzed for underlying DNA mutations using probe StB12.3 which detects insertions and methylation status of the FMR‐1 gene. All 3 showed an affected female genotype with a large insert (>500bp) and complete CpG island methylation.We conclude: (1) prenatally detected cytogenetic frequencies of females increase by an average 8.5 fold on follow‐up postnatal studies, (2) genetic counseling should indicate the risks to be affected are approximately 75% when a positive female is prenatally detected, (3) DNA testing can help determine carrier status but may not accurately predict whether a female will be me

ISSN:0148-7299    

DOI:10.1002/ajmg.1320430114

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractWe describe the neuropsychological and behavioral profiles of 48 critical members of a previously reported Sardinian pedigree [Filippi et al., 1991], in which the fully manifested Martin‐Bell syndrome (MBS), observed among males of the latest generations, is clearly the result of step‐wise mutational events occurred repeatedly along the X‐chromosome pathway linking all of them to a common ancestress, who must have been heterozygous for a fragile X (FRAX) premutation. We found that the unquestionable presence in the family of normal transmitting males and females could not be determined on the basis of neuropsychological and behavioral data alone. However, we think that the large variation observed in the expression of most diagnostic parameters among the MBS patients and their close female relatives in this family, could by itself be a connotation of the genome instability which characterizes the FRAX region in pedigrees segregating for the FRAX premutation(s) and mutati

ISSN:0148-7299    

DOI:10.1002/ajmg.1320430115

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractIn this paper we report the results of a brief examination of verbal learning and memory in 20 heterozygous fragile X [fra(X)] positive females and in 2 control groups of 20 subjects each. One control group was composed of fra(X)‐negative mothers (obligate carriers) and sisters of male probands with fra(X) syndrome, while the other consisted of 14 head injured and 6 learning disabled females. Intellectual functioning was assessed by means of the Wechsler scales, and learning was assessed by several different clinical memory tests. Significant differences were found between groups on measures of short‐term memory and learning efficiency. Groups did not differ on measures of cued recall or delayed recall. The findings are consistent with other data and suggest the possibility that central information processing and/or specific encoding processes are defective in persons with fra

ISSN:0148-7299    

DOI:10.1002/ajmg.1320430116

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

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 te

ISSN:0148-7299    

DOI:10.1002/ajmg.1320430117

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

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.

ISSN:0148-7299    

DOI:10.1002/ajmg.1320430118

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

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 min

ISSN:0148-7299    

DOI:10.1002/ajmg.1320430119

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractRecently, we detected fra(X)(q27.3) in aminocyte cultures from female identical twins. The pregnant woman did not exhibit fra(X)(q27.3) in whole blood cultures but was the sister of 2 affected brothers. DNA marker analyses showed that she was a carrier of FRAXA. Amniotic fluid cultures (AFCs) from twins A and B exhibited the fragile X [fra(X)] chromosome, but the level of cytogenetic expression was very low in twin A's AFCs. DNA marker studies indicated both twins were carriers of FRAXA. Peripheral umbilical blood sample (PUBS) cultures exhibited fra(X)(q27.3) at a frequency of about 10% for both twins. DNA fingerprinting indicated that the twins were identical, confirming the clinical impression, with a very thin separating amniotic membrane. To our knowledge, this is the only report of prenatal fra(X)(q27.3) detection in female identical twins, and the second report of identical twin detection [Rocchi et al., 1985].We have diagnosed prenatally fra(X)(q27.3) in 5 female fetuses using AFCs. The average fra(X) frequency was 4% for these positive female fetuses with a range of 0.5% to 8.5%. Follow‐up whole blood studies confirmed our original results at an average fra(X) frequency of 25%. In conclusion: 1. Low frequencies, perhaps 1 or 2%, or a few positive cells in AFCs, are likely to increase in magnitude when confirmed in whole blood cultures either pre‐ or postnatally. 2. It appears likely that the risk is low for false positive results in AFCs when low frequencies of fra(X)(q27.3) are encounte

ISSN:0148-7299    

DOI:10.1002/ajmg.1320430120

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

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 ce

ISSN:0148-7299    

DOI:10.1002/ajmg.1320430121

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY