Identification of genetic variations of a Chinese family with paramyotonia congenita via whole exome sequencing

Jinxin Li; Qinghai Huang; Liang Ge; Jing Xu; Xingjuan Shi; Wei Xie; Xiang Liu; Xiangdong Liu

doi:10.1016/j.gdata.2015.03.002

Identification of genetic variations of a Chinese family with paramyotonia congenita via whole exome sequencing

Genom Data. 2015 Mar 18:4:65-8. doi: 10.1016/j.gdata.2015.03.002. eCollection 2015 Jun.

Authors

Jinxin Li¹, Qinghai Huang¹, Liang Ge¹, Jing Xu¹, Xingjuan Shi¹, Wei Xie¹, Xiang Liu², Xiangdong Liu¹

Affiliations

¹ Key Laboratory of Developmental Genes and Human Diseases, Institute of Life Sciences, Southeast University, Nanjing 210096, China.
² Hainan Medical University, Hainan 571199, China.

Abstract

Paramyotonia congenita (PC) is a rare autosomal dominant neuromuscular disorder characterized by juvenile onset and development of cold-induced myotonia after repeated activities. The disease is mostly caused by genetic mutations of the sodium channel, voltage-gated, type IV, alpha subunit (SCN4A) gene. This study intended to systematically identify the causative genetic variations of a Chinese Han PC family. Seven members of this PC family, including four patients and three healthy controls, were selected for whole exome sequencing (WES) using the Illumina HiSeq platform. Sequence variations were identified using the SoftGenetics program. The mutation R1448C of SCN4A was found to be the only causative mutation. This study applied WES technology to sequence multiple members of a large PC family and was the first to systematically confirm that the genetic change in SCN4A is the only causative variation in this PC family and the SCN4A mutation is sufficient to lead to PC.

Keywords: Neuromuscular disorder; Paramyotonia congenita (PC); Sodium channel; Voltage-gated type IV alpha subunit (SCN4A); Whole exome sequencing (WES).