Chatkupt S, Lucek P R, Koenigsberger M R, Johnson W G
Neurosciences Department, University of Medicine and Dentistry of New Jersey, Newark.
Am J Med Genet. 1992 Nov 1;44(4):508-12. doi: 10.1002/ajmg.1320440426.
Fifty families (491 individuals in 137 sibships) with more than one living case of isolated, nonsyndromic spina bifida (SB) were analyzed genetically. There were twice as many gene-carrier females (56) as gene-carrier males (28) (P < 0.005). This was not an artifact of ascertainment bias because the sex ratio of gene-carriers was the same whether the pedigree was obtained through the proband's father or mother. Also, this effect was not observed in other disorders analyzed by the same method. Neither was the effect due to differential fertility because the number and sex of affected and unaffected children per gene-carrier parent were not different for male or female gene-carrier parents. There was no evidence that the missing male gene-carriers were lost by selective spontaneous abortion. There was no deficit of male-to-male or male-to-female transmission, excluding simple X-linked or simple mitochondrial inheritance. If genomic imprinting plays a role in the unequal female and male carrier frequencies in SB, penetrance should differ with parental sex. Penetrance was higher for offspring of female parents than of male parents, but the difference was not statistically significant. In addition, both male and female gene-carriers were frequently found in the same pedigree. Thus, the present data suggest a possible role for imprinting in SB.
对五十个家庭（137个同胞关系中的491人）进行了遗传学分析，这些家庭中存在不止一例孤立性、非综合征性脊柱裂（SB）存活病例。基因携带女性（56人）的数量是基因携带男性（28人）的两倍（P < 0.005）。这并非确定偏倚的人为现象，因为无论家系是通过先证者的父亲还是母亲获得，基因携带者的性别比例都是相同的。此外，在通过相同方法分析的其他疾病中未观察到这种效应。这种效应也不是由于生育差异造成的，因为每个基因携带父母的患病和未患病子女的数量及性别在男性和女性基因携带父母中并无差异。没有证据表明缺失的男性基因携带者因选择性自然流产而丢失。不存在男性对男性或男性对女性的传递缺陷，排除了简单的X连锁或简单的线粒体遗传。如果基因组印记在SB中女性和男性携带者频率不平等中起作用，外显率应因父母性别而异。女性父母的后代外显率高于男性父母的后代，但差异无统计学意义。此外，在同一个家系中经常发现男性和女性基因携带者。因此，目前的数据表明印记在SB中可能起作用。
