Sex Dev. 2019;13(1):26-34. doi: 10.1159/000494896. Epub 2018 Dec 1.
Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a disorder of sex development which affects 1 in 4,500 females and is characterized by agenesis of müllerian structures, including the uterus, cervix, and upper vagina. It can occur in isolation (type 1) or in conjunction with various anomalies (type 2), with a subset of these comprising müllerian, renal, and cervicothoracic abnormalities (MURCS) association. The genetic causes of MRKH have been investigated previously yielding limited results, with massive parallel sequencing becoming increasingly utilized. We sought to identify genetic contributions to MRKH using a combination of microarray and whole exome sequencing (WES) on a cohort of 8 unrelated women with MRKH and MURCS. WES data were analysed using a candidate gene approach to identify potential contributing variants. Microarray analysis identified a 0.6-Mb deletion in the previously implicated 16p11.2 region in a patient with MRKH type 2. WES revealed 16 rare nonsynonymous variants in MRKH candidate genes across the cohort. These included variants in several genes, such as LRP10 and DOCK4, associated with disorders with müllerian anomalies. Further functional studies of these variants will help to delineate their biological significance and expand the genotypic spectrum of MRKH.
Mayer-Rokitansky-Küster-Hauser (MRKH) 综合征是一种性发育障碍，影响每 4500 名女性中的 1 名，其特征为缪勒管结构的发育不全，包括子宫、宫颈和阴道上段。它可以单独发生（1 型）或与各种异常并存（2 型），其中一部分包括米勒管、肾脏和颈胸异常（MURCS）关联。MRKH 的遗传原因以前已经进行了研究，但结果有限，大规模平行测序的应用越来越广泛。我们使用微阵列和外显子组测序（WES）对 8 名无关联的 MRKH 和 MURCS 女性进行了组合研究，以确定遗传对 MRKH 的贡献。使用候选基因方法分析 WES 数据，以确定潜在的致病变异。微阵列分析在 1 名 2 型 MRKH 患者中鉴定出先前涉及的 16p11.2 区域的 0.6-Mb 缺失。WES 在整个队列中发现了 16 个罕见的 MRKH 候选基因非同义变异。这些变异包括与米勒管异常相关疾病的几个基因中的变异，如 LRP10 和 DOCK4。对这些变异的进一步功能研究将有助于阐明它们的生物学意义，并扩大 MRKH 的基因型谱。
