Institute of Human Genetics, Westfälische Wilhelms-University, Vesaliusweg 12-14, Münster 48149, Germany.
Hum Reprod. 2012 Sep;27(9):2872-5. doi: 10.1093/humrep/des206. Epub 2012 Jun 26.
The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by congenital aplasia of the uterus and the upper part of the vagina in women who usually have normal ovaries and a 46, XX karyotype. MRKH can occur as an isolated form (type I) or in combination with various malformations as a syndromic or a type II MRKH. To date, in most of the cases the underlying etiology remains unclear. Recently, in approximately 6% of MRKH patients, deletions of chromosomal region 17q12 have been identified. The LHX1 gene, which is located in the deletion interval, has been suggested to be a strong candidate, because targeting inactivation of Lhx1 causes a complex phenotype including aplasia of the Müllerian ducts.
By sequence analysis of LHX1 in a large cohort of MRKH patients, we detected a heterozygous frame shift mutation resulting in a premature stop codon. Previously, we have reported a heterozygous missense mutation of LHX1 in another MRKH patient.
We conclude that heterozygous mutations of LHX1 might be one cause of the MRKH syndrome in a subgroup of patients.
Mayer-Rokitansky-Küster-Hauser（MRKH）综合征的特征是女性子宫和阴道上段先天性发育不全，而这些女性通常具有正常的卵巢和 46,XX 核型。MRKH 可作为孤立形式（I 型）发生，也可与各种畸形结合作为综合征或 II 型 MRKH 发生。迄今为止，大多数情况下其潜在病因仍不清楚。最近，在大约 6%的 MRKH 患者中，已经确定了染色体 17q12 区域的缺失。位于缺失区间的 LHX1 基因被认为是一个强有力的候选基因，因为靶向 Lhx1 的失活会导致包括 Müllerian 管发育不全在内的复杂表型。
通过对一大群 MRKH 患者的 LHX1 进行序列分析，我们检测到一个杂合框移突变，导致提前终止密码子。之前，我们曾报道过另一位 MRKH 患者的 LHX1 杂合错义突变。
我们得出结论，LHX1 的杂合突变可能是一小部分患者 MRKH 综合征的一个原因。
