Sex Dev. 2019;13(1):35-40. doi: 10.1159/000496819. Epub 2019 Feb 9.
Müllerian anomalies comprise the Mayer-Rokitansky-Küster-Hauser syndrome as well as fusion defects of the müllerian ducts. Recurrent micro-aberrations like deletions in 16p11.2 encompassing TBX6 were found to be causative in these patients. TBX6 encodes a transcription factor which plays a role in paraxial mesoderm differentiation/specification. In previous studies, we and other groups found possibly pathogenic variants in TBX6 in patients with müllerian anomalies. Since we suggested TBX6 as a strong candidate, we performed sequential analysis of the TBX6 gene in additional 125 patients with müllerian anomalies, and 2 possibly pathogenic missense variants and 1 nonsense substitution in TBX6 in 4/125 patients were found. The missense variant c.484G>A, which we have described in a previous study, was reidentified but with no higher frequency as in our controls. We detected 3 possibly pathogenic variants in TBX6 and could show that the variant c.484G>A is not causative for disorders of the müllerian ducts in the non-Finnish European population. In summary, we present increasing evidence for association of variants in TBX6 with malformations of the müllerian ducts.
米勒管畸形包括 Mayer-Rokitansky-Küster-Hauser 综合征以及米勒管融合缺陷。在这些患者中，发现了反复出现的微缺失，如 16p11.2 缺失，其中包含 TBX6。TBX6 编码一种转录因子，在轴旁中胚层分化/特化中发挥作用。在之前的研究中，我们和其他研究小组在患有米勒管畸形的患者中发现了 TBX6 中可能致病的变异。由于我们将 TBX6 作为一个强有力的候选基因，我们在另外 125 名米勒管畸形患者中对 TBX6 基因进行了连续分析，在 4/125 名患者中发现了 TBX6 中的 2 个可能致病的错义变异和 1 个无义替换。我们在之前的研究中描述过的错义变异 c.484G>A 再次被识别，但在我们的对照组中没有更高的频率。我们在 TBX6 中检测到 3 个可能致病的变异，并证明变体 c.484G>A 不会导致非芬兰裔欧洲人群中米勒管的发育障碍。总之，我们提供了越来越多的证据表明 TBX6 中的变异与米勒管畸形有关。
