Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, 639 Zhizaoju Road, 200011, Shanghai, China.
BMC Pediatr. 2021 Jan 21;21(1):46. doi: 10.1186/s12887-021-02506-5.
Manitoba-oculo-tricho-anal (MOTA) syndrome is a rare syndrome with only 27 cases reported worldwide so far, but none was reported in the population of Eastern Asia. Such extremely low prevalence might be contributed by misdiagnosis due to its similarities in ocular manifestations with facial cleft. In our study, we discovered the first case of MOTA syndrome in the population of China, with 2 novel FRAS1 related extracellular matrix 1 (FREM1) gene stop-gain mutations confirmed by whole exome sequencing.
A 12-year-old Chinese girl presented with facial cleft-like deformities including aberrant hairline, blepharon-coloboma and broad bifid nose since birth. Whole exome sequencing resulted in the identification of 2 novel stop-gain mutations in the FREM1 gene. Diagnosis of MOTA syndrome was then established.
We discovered the first sporadic case of MOTA syndrome according to clinical manifestations and genetic etiology in the Chinese population. We have identified 2 novel stop-gain mutations in FREM1 gene which further expands the spectrum of mutational seen in the MOTA syndrome. Further research should be conducted for better understanding of its mechanism, establishment of an accurate diagnosis, and eventually the exploitation of a more effective and comprehensive therapeutic intervention for MOTA syndrome.
曼尼托巴眼-毛-肛（MOTA）综合征是一种罕见的综合征，迄今为止全球仅报告了 27 例病例，但在东亚人群中尚未报告。如此极低的患病率可能是由于其眼部表现与面裂相似而导致误诊所致。在我们的研究中，我们发现了首例 MOTA 综合征在中国人群中的病例，通过全外显子组测序证实了 2 个新型 FRAS1 相关细胞外基质 1（FREM1）基因的终止增益突变。
一名 12 岁的中国女孩自出生以来即存在面裂样畸形，包括异常发际线、眼睑裂-虹膜缺损和宽分叉鼻。全外显子组测序鉴定出 FREM1 基因中的 2 个新型终止增益突变。因此诊断为 MOTA 综合征。
我们根据临床表现和遗传病因在中国人群中发现了首例散发性 MOTA 综合征病例。我们在 FREM1 基因中发现了 2 个新型终止增益突变，进一步扩大了 MOTA 综合征中所见的突变谱。应进一步开展研究，以更好地了解其发病机制，建立准确的诊断方法，并最终为 MOTA 综合征开发更有效和全面的治疗干预措施。
