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Multiphasic analysis of whole exome sequencing data identifies a novel mutation of ACTG1 in a nonsyndromic hearing loss family

Gibeom Park1, Jungsoo Gim3, Ah Reum Kim2, Kyu-Hee Han2, Hyo-Sang Kim2, Seung-Ha Oh2, Taesung Park34, Woong-Yang Park67* and Byung Yoon Choi25*

Author Affiliations

1 Departments of Biomedical Sciences, Seoul National University Graduate School, 110-799, Seoul, Korea

2 Department of Otolaryngology, Seoul National University College of Medicine, 110-799, Seoul, Korea

3 Interdiciplinary Program for Bioinformatics, College of Natural Science, Seoul National University, 151-742, Seoul, Korea

4 Department of Statistics, College of Natural Science, Seoul National University, 151-742, Seoul, Korea

5 Department of Otolaryngology, Seoul National University Bundang Hospital, 463-707, Seongnam, Korea

6 Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, 135-710, Seoul, Korea

7 Translational Genomics Laboratory, Samsung Genome Institute, Samsung Medical Center, 135-710, Seoul, Korea

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BMC Genomics 2013, 14:191  doi:10.1186/1471-2164-14-191

Published: 18 March 2013



The genetic heterogeneity of sensorineural hearing loss is a major hurdle to the efficient discovery of disease-causing genes. We designed a multiphasic analysis of copy number variation (CNV), linkage, and single nucleotide variation (SNV) of whole exome sequencing (WES) data for the efficient discovery of mutations causing nonsyndromic hearing loss (NSHL).


From WES data, we identified five distinct CNV loci from a NSHL family, but they were not co-segregated among patients. Linkage analysis based on SNVs identified six candidate loci (logarithm of odds [LOD] >1.5). We selected 15 SNVs that co-segregated with NSHL in the family, which were located in six linkage candidate loci. Finally, the novel variant p.M305T in ACTG1 (DFNA20/26) was selected as a disease-causing variant.


Here, we present a multiphasic CNV, linkage, and SNV analysis of WES data for the identification of a candidate mutation causing NSHL. Our stepwise, multiphasic approach enabled us to expedite the discovery of disease-causing variants from a large number of patient variants.

Hearing loss; Copy number variation; Linkage analysis; Single nucleotide variation; Mutation analysis