Whole‑exome sequencing study identifies two novel rare variations associated with congenital talipes equinovarus.

Congenital talipes equinovarus (CTEV) is a common birth defect with an unclear genetic pathogenesis that results from both genetic and environmental factors. The present study aimed to identify novel variants in patients with CTEV using whole‑exome sequencing (WES) and to investigate the genetic factors responsible for the development of CTEV.A cohort of nine neonates/infants with suspected CTEV was recruited. Subsequently, sequential tests, including chromosome karyotyping and WES, were performed for each of the participants. Familial validation was performed using Sanger sequencing and low‑coverage copy‑number variation (CNV) sequencing. A novel CNV containing the mediator complex subunit 13L gene at 12q24.21‑q24.23 was detected by WES and further investigated by CNVseq. Additionally, a novel de novo missense variation, transforming growth factor‑β receptor 2: c.1280T>C, was identified by WES and further investigated by Sanger sequencing. The two identified variations were hypothesized to be causative genetic factors for the development of CTEV in the two cases the variations were identified in. In the present study, two pathogenic variations (one CNV and one single‑base variation) were detected in two Chinese families with CTEV. The results of the present study may aid in investigating the molecular basis of CTEV; however, further investigation is required.