Whole-exome sequencing for monozygotic twins discordant for hemifacial microsomia

Hemifacial microsomia (HFM) is the second most common congenital craniofacial malformation. Although many sporadic and familial cases have been studied to explore the etiology and pathogenesis of HFM, no common understanding has been reached. We aimed to further probe into the etiology of HFM through studying monozygotic twins. Here, we report two cases of pairs of monozygotic twins discordant for HFM, and performed whole-exome sequencing (WES) and bioinformatics analysis to help determine the underlying molecular mechanisms. We identified 93 and 83, and 101 and 104 genes containing rare germline mutations in the twins of the two pairs, respectively. No positive gene candidates were found among the samples, and none of the analyses results revealed a clear intersection with previously reported gene candidates. The pathogenesis of HFM twin pairs does not appear to be related to single nucleotide variants or small insertions/deletions. Thus, HFM may be caused by structure variations, epigenetic alterations, and/or instability of short repeat sequences, which requires further investigation in a larger cohort with sequencing technology for verification.