Massively Parallel Sequencing of a Chinese Family with DFNA9 Identified a Novel Missense Mutation in the LCCL Domain of COCH

Xiaodong Gu; Wenling Su; Mingliang Tang; Luo Guo; Liping Zhao; Huawei Li

doi:10.1155/2016/5310192

Massively Parallel Sequencing of a Chinese Family with DFNA9 Identified a Novel Missense Mutation in the LCCL Domain of COCH

Neural Plast. 2016:2016:5310192. doi: 10.1155/2016/5310192. Epub 2016 Dec 27.

Authors

Xiaodong Gu¹, Wenling Su², Mingliang Tang³, Luo Guo⁴, Liping Zhao⁴, Huawei Li⁵

Affiliations

¹ Otorhinolaryngology Department, Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200031, China; Key Laboratory of Hearing Medicine of National Health and Family Planning Commission, Shanghai 200031, China.
² Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital, Xiamen University, Xiamen, China.
³ Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
⁴ Otorhinolaryngology Department, Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200031, China; Key Laboratory of Hearing Medicine of National Health and Family Planning Commission, Shanghai 200031, China; Central Laboratory, Affiliated Eye and ENT Hospital, Fudan University, Shanghai 200031, China.
⁵ Otorhinolaryngology Department, Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200031, China; Key Laboratory of Hearing Medicine of National Health and Family Planning Commission, Shanghai 200031, China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China; Shanghai Engineering Research Center of Cochlear Implant, Shanghai 200031, China.

Abstract

DFNA9 is a late-onset, progressive, autosomal dominantly inherited sensorineural hearing loss with vestibular dysfunction, which is caused by mutations in the COCH (coagulation factor C homology) gene. In this study, we investigated a Chinese family segregating autosomal dominant nonsyndromic sensorineural hearing loss. We identified a missense mutation c.T275A p.V92D in the LCCL domain of COCH cosegregating with the disease and absent in 100 normal hearing controls. This mutation leads to substitution of the hydrophobic valine to an acidic amino acid aspartic acid. Our data enriched the mutation spectrum of DFNA9 and implied the importance for mutation screening of COCH in age related hearing loss with vestibular dysfunctions.

MeSH terms

Amino Acid Sequence
Asian People / genetics*
Extracellular Matrix Proteins / genetics*
Female
Hearing Loss, Sensorineural / diagnosis
Hearing Loss, Sensorineural / genetics*
High-Throughput Nucleotide Sequencing / methods*
Humans
Male
Mutation, Missense / genetics*
Pedigree
Protein Domains / genetics
Sequence Analysis, DNA / methods

Substances

COCH protein, human
Extracellular Matrix Proteins

Supplementary concepts

Deafness, Autosomal Dominant 9
Nonsyndromic sensorineural hearing loss