Novel and recurrent MYO7A mutations in Usher syndrome type 1 and type 2

Weining Rong; Xue Chen; Kanxing Zhao; Yani Liu; Xiaoxing Liu; Shaoping Ha; Wenzhou Liu; Xiaoli Kang; Xunlun Sheng; Chen Zhao

doi:10.1371/journal.pone.0097808

Novel and recurrent MYO7A mutations in Usher syndrome type 1 and type 2

PLoS One. 2014 May 15;9(5):e97808. doi: 10.1371/journal.pone.0097808. eCollection 2014.

Authors

Weining Rong¹, Xue Chen², Kanxing Zhao³, Yani Liu¹, Xiaoxing Liu⁴, Shaoping Ha¹, Wenzhou Liu¹, Xiaoli Kang⁵, Xunlun Sheng¹, Chen Zhao⁶

Affiliations

¹ Ningxia Eye Hospital, Ningxia People's Hospital, Ningxia, China.
² Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, State Key Laboratory of Reproductive Medicine, Nanjing, China; Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
³ Tianjin Medical University, Tianjin Eye Hospital, Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin, China.
⁴ Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, State Key Laboratory of Reproductive Medicine, Nanjing, China.
⁵ Department of Ophthalmology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁶ Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, State Key Laboratory of Reproductive Medicine, Nanjing, China; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat Sen University, Guangzhou, China.

Abstract

Usher syndrome (USH) is a group of disorders manifested as retinitis pigmentosa and bilateral sensorineural hearing loss, with or without vestibular dysfunction. Here, we recruited three Chinese families affected with autosomal recessive USH for detailed clinical evaluations and for mutation screening in the genes associated with inherited retinal diseases. Using targeted next-generation sequencing (NGS) approach, three new alleles and one known mutation in MYO7A gene were identified in the three families. In two families with USH type 1, novel homozygous frameshift variant p.Pro194Hisfs*13 and recurrent missense variant p.Thr165Met were demonstrated as the causative mutations respectively. Crystal structural analysis denoted that p.Thr165Met would very likely change the tertiary structure of the protein encoded by MYO7A. In another family affected with USH type 2, novel biallelic mutations in MYO7A, c.[1343+1G>A];[2837T>G] or p.[?];[Met946Arg], were identified with clinical significance. Because MYO7A, to our knowledge, has rarely been correlated with USH type 2, our findings therefore reveal distinguished clinical phenotypes associated with MYO7A. We also conclude that targeted NGS is an effective approach for genetic diagnosis for USH, which can further provide better understanding of genotype-phenotype relationship of the disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Base Sequence
DNA Mutational Analysis
Female
Fundus Oculi
Genetic Association Studies
Humans
Male
Middle Aged
Models, Molecular
Mutation, Missense*
Myosin VIIa
Myosins / chemistry
Myosins / genetics*
Pedigree
Protein Structure, Secondary
Protein Structure, Tertiary
Usher Syndromes / genetics*
Young Adult

Substances

MYO7A protein, human
Myosin VIIa
Myosins

Grants and funding

This work was supported by National Key Basic Research Program of China (973 Program, 2013CB967500); National Natural Science Foundation of China (81222009, 81170856, 81160124, 81260154, and 81170867); Thousand Youth Talents Program of China (to CZ); Jiangsu Outstanding Young Investigator Program (BK2012046); Jiangsu Province’s Key Provincial Talents Program (RC201149); the Fundamental Research Funds of the State Key Laboratory of Ophthalmology (to CZ); Jiangsu Province’s Scientific Research Innovation Program for Postgraduates (CXZZ13_05 to XC); Applied Research Program of the Science and Technology Commission Foundation of Tianjin (013111411 to KZ); and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.