Department of Auricular Reconstruction, Chinese Academy of Medical Sciences and Peking Union Medical College Plastic Surgery Hospital, Beijing, China.
Department of Plastic Surgery, Affiliated Hospital of Weifang Medical University, Weifang, China.
Mol Genet Genomic Med. 2021 May;9(5):e1657. doi: 10.1002/mgg3.1657. Epub 2021 Apr 3.
Microtia is a congenital malformation of the external ear and may occur as an isolated deformity or as part of a syndrome. Our previous study found a high correlation between microtia and thoracic deformities, thus, we propose that external ear and thorax development may be regulated by certain genes in common.
We performed exome sequencing on 10 families of sporadic microtia with thoracic abnormalities. We identified mutated genes under different models of inheritance, and checked them through Mouse Genome Informatics and association analysis.
We identified 45 rare mutations, including 9 de novo mutations, 20 heterozygous mutations, 3 homozygous mutations, and 13 hemizygous mutations, of which 2 are likely to be causative. They are de novo missense variant in PHF5A and compound heterozygous mutations in CYP26B1, of which CYP26B1 mutation is highly likely pathogenic.
The results indicate that certain genes may affect both external ear and thorax development, and demonstrate the benefits of whole-exome sequencing in identifying candidate genes of microtia. This study provides a new way for genetic exploration in microtia.
小耳畸形是一种外耳先天性畸形，可作为孤立性畸形发生，也可作为综合征的一部分发生。我们之前的研究发现小耳畸形与胸廓畸形之间存在高度相关性，因此，我们提出外耳和胸廓的发育可能受到某些共同基因的调控。
我们对 10 个具有胸廓异常的散发小耳畸形家系进行了外显子组测序。我们在不同的遗传模式下鉴定出了突变基因，并通过 Mouse Genome Informatics 和关联分析进行了验证。
我们鉴定出了 45 个罕见突变，包括 9 个新生突变、20 个杂合突变、3 个纯合突变和 13 个半合子突变，其中 2 个可能是致病突变。它们是 PHF5A 中的新生错义变异和 CYP26B1 中的复合杂合突变，其中 CYP26B1 突变极有可能是致病的。
这些结果表明，某些基因可能同时影响外耳和胸廓的发育，并证明了全外显子组测序在鉴定小耳畸形候选基因方面的优势。本研究为小耳畸形的遗传探索提供了一种新方法。
