A novel frameshift mutation of SMPX causes a rare form of X-linked nonsyndromic hearing loss in a Chinese family

Zhijie Niu; Yong Feng; Lingyun Mei; Jie Sun; Xueping Wang; Juncheng Wang; Zhengmao Hu; Yunpeng Dong; Hongsheng Chen; Chufeng He; Yalan Liu; Xinzhang Cai; Xuezhong Liu; Lu Jiang

doi:10.1371/journal.pone.0178384

A novel frameshift mutation of SMPX causes a rare form of X-linked nonsyndromic hearing loss in a Chinese family

PLoS One. 2017 May 25;12(5):e0178384. doi: 10.1371/journal.pone.0178384. eCollection 2017.

Authors

Zhijie Niu^{1

2

3}, Yong Feng^{1

2

4}, Lingyun Mei^{1

2}, Jie Sun^{1

2}, Xueping Wang^{1

2}, Juncheng Wang^{1

2}, Zhengmao Hu⁴, Yunpeng Dong³, Hongsheng Chen^{1

2}, Chufeng He^{1

2}, Yalan Liu^{1

2}, Xinzhang Cai^{1

2}, Xuezhong Liu^{1

3}, Lu Jiang^{1

2}

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, PR China.
² Key Laboratory of Otolaryngology Major Disease Research of Hunan Province, Changsha, PR China.
³ Department of Otolaryngology (D-48), University of Miami Miller School of Medicine, Miami, FL, United States of America.
⁴ State Key Laboratory of Medical Genetics, Central South University, Changsha, PR China.

Abstract

X-linked hearing impairment is the rarest form of genetic hearing loss (HL) and represents only a minor fraction of all cases. The aim of this study was to investigate the cause of X-linked inherited sensorineural HL in a four-generation Chinese family. A novel duplication variant (c.217dupA, p.Ile73Asnfs*5) in SMPX was identified by whole-exome sequencing. The frameshift mutation predicted to result in the premature truncation of the SMPX protein was co-segregated with the HL phenotype and was absent in 295 normal controls. Subpopulation screening of the coding exons and flanking introns of SMPX was further performed for 338 Chinese patients with nonsydromic HL by Sanger sequencing, and another two potential causative substitutions (c.238C>A and c.55A>G) in SMPX were identified in additional sporadic cases of congenital deafness. Collectively, this study is the first to report the role of SMPX in Chinese population and identify a novel frameshift mutation in SMPX that causes not only nonsyndromic late-onset progressive HL, but also congenital hearing impairment. Our findings extend the mutation and phenotypic spectrum of the SMPX gene.

MeSH terms

Adolescent
Adult
Asian People / genetics*
Child
Child, Preschool
Deafness / genetics*
Exome / genetics
Exons / genetics
Female
Frameshift Mutation / genetics*
Genes, X-Linked / genetics*
Hearing Loss / genetics*
Hearing Loss, Sensorineural / genetics
Humans
Infant
Male
Middle Aged
Muscle Proteins / genetics*
Pedigree
Young Adult

Substances

Muscle Proteins
SMPX protein, human

Supplementary concepts

Nonsyndromic Deafness

Grants and funding

This work was supported by the National 973 Basic Research Program of China (Grant Nos. 2014CB541702 and 2014CB943003); National Natural Science Foundation of China (Grant Nos. 81500803, 81470705, and 81300833); and Science and Technology Projects in Hunan Province (Grant No. 13JJ4023). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.