ISSN:0148-7299    

DOI:10.1002/ajmg.1320300102

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

年代:1988

数据来源: WILEY

ISSN:0148-7299    

DOI:10.1002/ajmg.1320300103

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

年代:1988

数据来源: WILEY

摘要:

AbstractA small series of male and female fra(X) positive children is reviewed retrospectively clinically and photographically to identify a profile of age‐related manifestations and behavioral traits of predictive value.This method involves a crossmatch with the cases and trait lists in the POSSUM Data Base. The plan then is to test the sensitivity and specificity in a prospective series. If this proves reliable, a request for a fra(X) cytogenetic analysis could be limited to the clinically screened matching cases, rather than the present costly exercise of testing all undiagnosed intellectually handicapped childre

ISSN:0148-7299    

DOI:10.1002/ajmg.1320300104

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

年代:1988

数据来源: WILEY

摘要:

AbstractA review of the Leuven data on the fragile X syndrome indicates that sudden infant death is frequently observed in the progeny of obligate female carriers. This observation may be another indication of a central nervous dysfunction in infants with this type of X‐linked mental retardatio

ISSN:0148-7299    

DOI:10.1002/ajmg.1320300105

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

年代:1988

数据来源: WILEY

摘要:

AbstractAmong 100 males with fragile X [fra(X)] or Martin‐Bell syndrome, two have developed malignancies. The first case, a 57‐year‐old man with fra(X) expression in 12% of peripheral blood lymphocytes, developed a seminoma of the left testis at age 45 years and in the right testis at age 50 years. The second case, a 16‐year‐old white boy with fra(X) expression in 23% of lymphocytes, developed a mucin‐producing adenocarcinoma of the colon at age 14 years. Because of the unusual nature of the tumors observed in these patients and in 2 other patients from the literature, we suggest that individuals with the fra(X) syndrome may be at increased ris

ISSN:0148-7299    

DOI:10.1002/ajmg.1320300106

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

年代:1988

数据来源: WILEY

摘要:

AbstractAn 18‐year‐old mentally retarded male with the Martin‐Bell syndrome was fragile X positive. He died suddenly with viral pneumonia and myocarditis. At autopsy, generalized tubular hypoplasia of the aorta and a mild coarctation were discovered. The base of the mitral and tricuspid valves showed striking aberrations in elastin distribution and structure by light microscopy. Local collagen alterations were also noted. Comparable changes were seen in the skin elastin as well as a severe depletion of acid mucopolysaccharides. These changes suggest a structural disruption underlying the clinical connective tissue problems in some patients with the fragile X syn

ISSN:0148-7299    

DOI:10.1002/ajmg.1320300107

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

年代:1988

数据来源: WILEY

摘要:

AbstractTo date the concurrent presence of the fragile‐X and the Klinefelter syndromes in the same individual has been found at least 8 times either in the course of screening for the fra(X) condition in mentally retarded males or among the relatives of fra(X) propositi. Given the high frequency of both events in the general population and the heterogeneous approaches with which the above cases were ascertained, it has not been possible to determine unequivocally so far whether the finding is purely coincidental or the expression of some underlying biological relationship. To evaluate the issue, we have screened a large population of institutionalized mentally retarded males for microorchidism, and submitted to a full karyotype analysis and fra(X) testing the patients that were found to have marked bilateral microorchidism. Thus, in a total of 32 microorchidism patients identified among 1115 mentally retarded males, we found 6 to have a 47,XXY chromosome complement in all (or in most) of their cells, with one of them having also the fra(X) marker in 9% of the metaphases examined. In addition, another bearer of the fra(X) marker (but only in 4% of his metaphases) was found among 26 47, XXY mentally normal males ascertained throughout routine cytogenetic analysis of males with microorchidism referred to our genetic counseling unit during the last 10 years. In our laboratory the fra(X) marker has never been observed with such a frequency inatotal of several hundred normal XY males and XX females studied as control cases in the course of previously reported family and population studies. Taken at their face value, the present findings suggest that the incidence of the fra(X) marker among mentally retarded 47, XXY males (and possibly among 47, XXY individuals in general) is several fold greater than the incidence reported, for XY males and XX females. One of the most economical inter pretations of these observations is that heterozygosity for the fra(X) mutation may be a major cause of meiotic X chromosome non‐disjunction. If confirmed, this attractive hypothesis is likely to provide new clues for investigating the biology of the fra(X) mutation and its relationship ‐ if any ‐ with the mechanisms of normal and aberrant

ISSN:0148-7299    

DOI:10.1002/ajmg.1320300108

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

年代:1988

数据来源: WILEY

摘要:

AbstractIn this paper we report on a third patient with Klinefelter syndrome and fragile X. In the Leuven experience the simultaneous occurrence of both conditions is 1:155 (3 fra(X) positive Klinefelter patients in a total number of 465 fra(X) positive males), a concurrence much higher than expected by chance considering the frequency of both conditions.

ISSN:0148-7299    

DOI:10.1002/ajmg.1320300109

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

年代:1988

数据来源: WILEY

摘要:

AbstractThe possibility that female carriers of the fragile X gene(s) are at increased risk for nondisjunctional events leading to aneuploid offspring has been suggested by several investigators. To better address this question we analyzed pedigrees of 117 families in which the fragile X syndrome is segregating.The 117 pedigrees, originally collected for segregation analyses, included 236 females with offspring whose carrier status was determined by cytogenetic or pedigree analysis or by analyses using flanking DNA markers. These 236 females have had 931 offspring including one 47, XXY and 6 trisomy 21 individuals (1/155). Statistical analysis suggested that the observed rate of trisomy 21 was significantly higher than expected (Fisher's exact test, p 0.05). Assuming a Poisson distribution to calculate the confidence interval for the observed rate of trisomy 21 individuals, we found that the expected rate of 1.6/1000 in this sample fell outside the 99% confidence limits of our observed rate of 1/155. Additional data from a larger sample are needed to replicate these findings.

ISSN:0148-7299    

DOI:10.1002/ajmg.1320300110

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

年代:1988

数据来源: WILEY

摘要:

AbstractWe collected data on growth, psychomotor development, speech and language development, and intellectual function on a cohort of 100 males with the fragile X chromosome and 95 carrier females. The data include information on prenatal growth (33 males), growth during the preadult years (32 males), psychomotor development during the first 2 years (25 males), speech and language development (15 males and 5 females), and intellectual function (93 males, 33 females, and 10 obligate carriers who were cytogenetically normal). Birth measurements appeared normal when plotted on the Usher/McLean curves of newborn infants (mean head circumference ‐ OFC ‐ at 40th centile, length at 60th centile and weight at 55th centile). Following birth, OFC rose above the 50th percentile and continued above average throughout the preadult years, whereas average length was above average for the first 5 years only and weight did not deviate from the normal mean. Psychomotor development lagged behind the norm from birth with affected males requiring nearly twice as long as expected to sit alone, walk unassisted, and say first words clearly. All males and females studied had significant language delay; all except one male had abnormalities of articulation. All on whom a clear voice sample was obtained had low voice pitch, and 80% had a hoarse or harsh quality of voice. Five males had word repetitions or perseverative speech during the preadult years. The mean IQ of the 93 males studied was 33 and regression analysis demonstrated a decrease in intellectual performance with age. Four fifths of the female carriers who expressed the fra(X) had intell‐ectual performance in the mentally retarded range and showed similar decrease in performance with age. Obligate female carriers who did not express the fra(X) site had normal IQs (IQ 102 ±

ISSN:0148-7299    

DOI:10.1002/ajmg.1320300111

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

年代:1988

数据来源: WILEY