Whole‐exome sequencing analysis in 10 families of sporadic microtia with thoracic deformities

Background 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. Methods 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. Results 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. Conclusion 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. Whole‐exome sequencing analysis, ten families of sporadic microtia; microtia with thoracic deformities.