THE ETIOLOGY OF MALENESS IN XX MEN
THE ETIOLOGY OF MALENESS IN XX MEN
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DOI：
10.1007/bf00284157
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发表时间：
1981-01-01
期刊：
影响因子：
5.3
通讯作者：
DELACHAPELLE, A
中科院分区：
文献类型：
--
作者：
DELACHAPELLE, A
回顾了与人类XX男性的病因学相关的信息。与对照男性和一级男性亲属相比，患者身高较低，牙齿较小，这可能意味着患者从未携带任何Y染色体。无论是关于Y染色体偶尔有丝分裂的报道，还是在Sertoli细胞中出现Y染色质的报道，都不足以令人信服地支持低级别或限制性嵌合体是常见病因的观点。关于XX男性其中一条X染色体长度增加的报道很少，有些是相互矛盾的。也没有任何证据支持物质损失的想法。然而，没有可见的细胞遗传学改变并不排除易位、交换或缺失的可能性。孟德尔基因突变可能解释了XX雄性的一些例子，类似的基因在几个动物物种中是众所周知的。人类XX男性患病率的地理差异可以用基因频率的差异来解释。但是，如果基因突变是XX男性的常见原因，那么会有更多的家族性病例。任何解释XX男性病因的假说都应该考虑以下事实。至少有4例XX男性遗传了他们父亲携带的xG等位基因，至少有9例没有。XX男性的xG表型频率比女性更接近男性，而不存在色盲的XX男性(在40名受试者中)的分布与女性相似。此外，在XX男性中存在H-Y抗原，其强度通常介于正常男性和女性之间。最后，在一个由三个独立确定的XX男性组成的家系中，三个男性的母亲都是H-Y抗原阳性，其中两个的H-Y抗原遗传模式排除了X染色体的传递。许多数据与Y染色体上决定睾丸的基因和含有xG基因的X染色体的一部分互换而产生XX男性的假设一致。然而，支持这一假说的实际证据仍然缺乏，H-Y抗原数据也不容易解释。相反，如果最近关于控制H-Y抗原表达的机制的假设得到证实，那么对睾丸决定起负控制作用的基因将位于X染色体短臂末端附近。这个假定的基因在正常女性中被认为没有失活，因为至少有两个位于同一区域的其他基因，即Xgandsterid硫酸酯酶，没有失活。这些基因座的缺失或失活将解释XX男性的产生，并与大多数但不是全部的事实相一致。目前还没有一个单一的假设本身可以解释关于XX男性积累的所有事实。虽然嵌合体在大多数情况下看起来非常不可能，但孟德尔基因突变、易位、X-Y交换、X染色体的微小缺失或优先失活，或其部分，仍然是可能的。XX男性的病因很可能是异质性的。
Information relating to the etiology of human XX males is reviewed. The lesser body height and smaller tooth size in comparison with control males and first-degree male relatives could imply that the patients never had any Y chromosome. Neither reports of occasional mitoses with a Y chromosome, nor of the occurrence of Y chromatin in Sertoli cells are convincing enough to support the idea that low-grade or circumscribed mosaicism is a common etiologic factor. Reports of an increase in length of one of the X chromosomes in XX males are few and some are conflicting. Nor is there any evidence to support the idea of loss of material. However, absence of visible cytogenetic alteration does not rule out the possibility of translocations, exchanges or deletions.A few familial cases are known. Mendelian gene mutations may account for a number of instances of XX males, similar genes being well known in several animal species. The existing geographical differences in the prevalence of human XX males could be explained by differences in gene frequency. But if gene mutation were a common cause of XX maleness there would be more familial cases.Any hypothesis explaining the etiology of XX males should take into account the following facts. There are at least 4 examples of XX males who have inherited the Xg allele carried by their fathers, and at least 9 of such males who have not. The frequency of the Xg phenotype among XX males is far closer to that of males than to that of females, while the absence of any color-blind XX males (among 40 tested) resembles the distribution in females. Furthermore, H-Y antigen is present in XX males, often at a strength intermediate between that in normal males and females. Finally, in a pedigree comprising three independently ascertained XX males, the mothers of all three are H-Y antigen-positive, and the pattern of inheritance of the antigen in two of them precludes X-chromosomal transmission.Many of the data are consistent with the hypothesis that XX males arise through interchange of the testic-determining gene on the Y chromosome and a portion of the X chromosome containing the Xg gene. However, actual evidence in favor of this hypothesis is still lacking, and the H-Y antigen data are not easy to explain. In contrast, if recent hypotheses on the mechanisms controlling the expression of H-Y antigen are confirmed, a gene exerting negative control on testis determination would be located near the end of of the short arm of the X chromosome. This putative gene is believed not to be inactivated in normal females, for at least two other genes located in the same region, i.e.Xgandsteroid sulfatase, are not. Deletion or inactivation of these loci would explain how XX males arise and would be consistent with most, but not all, the facts.There is yet no single hypothesis that by itself can explain all the facts accumulated about XX males. While mosaicism appears very unlikely in most cases, Mendelian gene mutation, translocation, X-Y interchange, a minute deletion or preferential inactivation of an X chromosome, or part thereof, remain possible. The etiology of XX maleness may well be heterogeneous.