脆性X综合征的细胞遗传学研究

本研究从１０个Ｘ－连锁智力低下家系中，经细胞遗传学检查，检测出５个Ｆｒａ（Ｘ）综合征家系，共１５名患者和携带者检查发现：１、不同成份培养液对脆性Ｘ表达有影响。２、活性Ｘ染色体Ｘｑ２７迟复制与Ｆｒａ（Ｘ）综合征患者智力密切相关。３、Ｆｒａ（Ｘ）染色体的活性与女性携带者的智力有一定的关系

Cytogenetic study of fragile X syndrome

The fragile X syndrome fra(X) s] is the most common type of X-linked mental retardations(XLMR),the estimated frequency is 1/2,000 in males.The inheritance pattern is very complicated ,although the cytogenetic marker fra(X)(fragile site at Xq27)can be detected in most fra(X) s patients, some patients and female carriers are fra(X)negative,the fra(X)gene may also be transmitted through phenotypically and cytologically normal males(transmitting males).This unique inheritance was explained by an germ-line imprinting hypothesis by some authors.This study was initiated to investigate:1.proportion of fra(X)s in XLMR;2.effects of cultural conditions on the expression of fra(X);3.correlation of fra(X)on the active X chromosome to IQ in female carriers;4,roles of late replication at Xq27 in the causition of mental retardation.Chromosome analysis detected five fra(X)s in ten XLMR families ascertained through population survey.15 patients carriers constituted the subjects of our further cytogenetic study.The averages of expression rates of fra(X)in these subjects were 6. 71% and 10.94% in the mediums of TC199 BrdU and TC199 BrdU FudR respectively,which indicates that the fra(X)may be enhanced by FudR ,an inhibitor of thymidine synthesis.The proportion of fra(X)residing in the active X chromosomes was 72% in the affected females,and was 28% in normal female carriers.The late replication at Xq27 on the active X chromosomes was detected in 9.1% of calls of the affected patients and female carriers,and in 2.3% of the cells in the control group.