Imbeaud S, Carré-Eusèbe D, Rey R, Belville C, Josso N, Picard J Y
Unité de Recherches sur l'Endocrinologie du Développement (INSERM) Ecole Normale Supérieure, Département de Biologie, Montrouge, France.
Hum Mol Genet. 1994 Jan;3(1):125-31. doi: 10.1093/hmg/3.1.125.
A rare form of familial male pseudohermaphroditism, the persistent Müllerian duct syndrome (PMDS) is characterized by persistence of uterus and Fallopian tubes in 46,XY phenotypic males and is ascribed to defects in the synthesis or action of anti-Müllerian hormone (AMH). Biologically, PMDS is heterogeneous: in some cases, bioactive AMH is normally expressed by testicular tissue while, in others, no AMH is produced, suggesting the possibility of an AMH gene mutation, several of which have already been described. Molecular analysis of the AMH gene has now been performed in 21 additional patients and their families. In 6 patients, with normal serum concentration of AMH, the AMH gene was normal or contained only polymorphisms and silent mutations, supporting the hypothesis that the condition is due to end-organ resistance. Nine novel mutations were discovered in the remaining subjects, with low or undetectable levels of serum AMH. These mutations, when present in homozygotes or compound heterozygotes, were associated with the PMDS phenotype, the same mutation never being observed in two different families. The three first exons of the AMH gene appear particularly mutation-prone, although they are less GC rich than the 2 last ones and code for the N-terminal part of the AMH protein, which is not in itself essential to bioactivity.
持续性苗勒管综合征（PMDS）是一种罕见的家族性男性假两性畸形，其特征是46,XY表型男性的子宫和输卵管持续存在，这归因于抗苗勒管激素（AMH）合成或作用的缺陷。从生物学角度来看，PMDS具有异质性：在某些情况下，生物活性AMH由睾丸组织正常表达，而在其他情况下，则不产生AMH，这提示了AMH基因突变的可能性，其中一些突变已经被描述。现在已经对另外21名患者及其家族进行了AMH基因的分子分析。在6名血清AMH浓度正常的患者中，AMH基因正常或仅包含多态性和沉默突变，支持了该病是由于终末器官抵抗的假说。在其余血清AMH水平低或检测不到的受试者中发现了9种新的突变。这些突变在纯合子或复合杂合子中出现时，与PMDS表型相关，在两个不同家族中从未观察到相同的突变。AMH基因的前三个外显子似乎特别容易发生突变，尽管它们的GC含量低于最后两个外显子，并且编码AMH蛋白的N端部分，而该部分本身对生物活性并非必不可少。
