Sherman S L, Morton N E, Jacobs P A, Turner G
Ann Hum Genet. 1984 Jan;48(1):21-37. doi: 10.1111/j.1469-1809.1984.tb00830.x.
The results of a cytogenetic and segregation analysis of 110 pedigrees of the mar (X) syndrome are reported. The cytogenetic study indicated an inverse relationship between IQ and the mar(X) frequency in females but not in males. A small but significant effect of age on mar(X) frequency was observed in both males and females, but in females it was restricted to those of normal intelligence, retarded females showing no significant effect. Classical segregation analysis was performed using the program SEGRAN, analysing sexes separately. A 20% deficit of affected males was observed, the most plausible explanation for the majority of these cases being incomplete penetrance. Since this was an unexpected result, the data were scrutinized for possible biases; however, correction of these had little effect on the estimate. The penetrance of mental impairment in carrier females was estimated to be 30% and of mental impairment and/or mar(X) expression to be 56%. Thus 44% of carriers cannot be detected with our definition of affection. No evidence for sporadic cases among affected males was found. Complex segregation analysis was performed using the sex-linked version of POINTER, analysing sexes together. This was done in order to test the results from classical segregation analysis, to test for family resemblance and to estimate mutation rates. It was confirmed that there was a 20% deficit of affected males, that penetrance of mental impairment in females was approximately 30% and that there was no evidence for sporadic males. Thus all males with the gene appear to have received it from their carrier mothers and all mutations must occur in sperm. The mutation rate in sperm was estimated to be as high as 7.2 X 10(-4), implying that over one-half of random carrier females are fresh mutants. Our results have important implications for genetic counseling as they imply that all mothers of isolated affected males are carriers, that normal brothers of affected males have a 17% chance of carrying the gene and transmitting it to all their daughters, and that normal sisters of affected males have, at most, a 30% chance of being carriers. Since there are biases in the data due to the testing of particular individuals, these probabilities must be considered approximations until they are independently confirmed.
报告了110个mar(X)综合征家系的细胞遗传学和分离分析结果。细胞遗传学研究表明，女性智商与mar(X)频率呈负相关，而男性则不然。在男性和女性中均观察到年龄对mar(X)频率有微小但显著的影响，但在女性中，这种影响仅限于智力正常者，智力发育迟缓的女性未显示出显著影响。使用SEGRAN程序进行经典分离分析，分别对性别进行分析。观察到受影响男性有20%的不足，对这些病例中的大多数最合理的解释是不完全外显率。由于这是一个意外结果，对数据进行了仔细检查以查找可能的偏差；然而，对这些偏差进行校正对估计值影响不大。携带致病基因女性的精神障碍外显率估计为30%，精神障碍和/或mar(X)表达的外显率估计为56%。因此，根据我们对患病的定义，44%的携带者无法被检测到。在受影响男性中未发现散发病例的证据。使用POINTER的性连锁版本进行复杂分离分析，对性别进行综合分析。这样做是为了检验经典分离分析的结果，检验家族相似性并估计突变率。证实了受影响男性有20%的不足，女性精神障碍的外显率约为30%，且没有散发性男性的证据。因此，所有携带该基因的男性似乎都从其携带致病基因的母亲那里遗传了该基因，并且所有突变都必定发生在精子中。精子中的突变率估计高达7.2×10⁻⁴，这意味着超过一半的随机携带致病基因的女性是新的突变体。我们的结果对遗传咨询具有重要意义，因为这意味着所有孤立的受影响男性的母亲都是携带者，受影响男性的正常兄弟有17%的机会携带该基因并将其传给所有女儿，而受影响男性的正常姐妹最多有30%的机会成为携带者。由于由于对特定个体进行检测，数据存在偏差，在这些概率得到独立证实之前，必须将其视为近似值。
