Target region capture sequencing for detecting GDAP1 gene mutation of autosomal recessive Charcot-Marie-Tooth disease

Abstract

Background Owing to the clinical variability and molecular heterogeneity, the traditional Sanger sequencing takes time and effort and is inefficient. In this paper, target region capture sequencing in the diagnosing of autosomal recessive Charcot-Marie-Tooth disease (AR-CMT) is explored.  Methods Clinical data and peripheral blood sample of 5 clinically suspected AR - CMT patients were collected. Charcot-Marie-Tooth disease (CMT) related gene mutation were detected by target region capture sequencing. The candidate variants were confirmed in the peripheral blood sample of the patients and their parents by Sanger sequencing. Results Target region capture sequencing revealed that compound heterozygous mutations of GDAP1 gene was found in 2 patients, and was not seen in the other 3 patients. Sanger sequencing revealed that among the 2 patients with mutation of GDAP1 gene, compound heterozygous mutation c.767A > G (p. His256Arg) and c.866T > A (p. Phe289Tyr) were seen in Case 1, whose father carried c.866T > A (p. Phe289Tyr) heterozygous mutation and mother carried c.767A > G (p. His256Arg) heterozygous mutation, while compound heterozygous mutation c.571C > T (p. Arg191X) and c.589delC (p. Asp198IlefsX8) were seen in Case 2, whose father carried c.589delC (p. Asp198IlefsX8) heterozygous mutation and mother carried c.571C > T (p. Arg191X) heterozygous mutation. Therefore, Case 1 and Case 2 were all diagnosed as AR-CMT. Conclusions Target region capture sequencing is a rapid and reliable genetic testing method with high efficiency. It is applicable for the diagnosis of AR-CMT.

DOI: 10.3969/j.issn.1672-6731.2017.08.009