Exome sequencing identifies a novel CEACAM16 mutation associated with autosomal dominant nonsyndromic hearing loss DFNA4B in a Chinese family

Honghan Wang, Xinwei Wang, Chufeng He, Haibo Li, Jie Qing, M'hamed Grati, Zhengmao Hu, Jiada Li, Yiqiao Hu, Kun Xia, Lingyun Mei, Xingwei Wang, Jianjun Yu, Hongsheng Chen, Lu Jiang, Yalan Liu, Meichao Men, Hailin Zhang, Liping Guan, Jingjing XiaoJianguo Zhang, Xuezhong Liu, Yong Feng

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Autosomal dominant nonsyndromic hearing loss (ADNSHL/DFNA) is a highly genetically heterogeneous disorder. Hitherto only about 30 ADNSHL-causing genes have been identified and many unknown genes remain to be discovered. In this research, genome-wide linkage analysis mapped the disease locus to a 4.3 Mb region on chromosome 19q13 in SY-026, a five-generation nonconsanguineous Chinese family affected by late-onset and progressive ADNSHL. This linkage region showed partial overlap with the previously reported DFNA4. Simultaneously, probands were analyzed using exome capture followed by next-generation sequencing. Encouragingly, a heterozygous missense mutation, c.505G>A (p.G169R) in exon 3 of the CEACAM16 gene (carcinoembryonic antigen-related cell adhesion molecule 16), was identified via this combined strategy. Sanger sequencing verified that the mutation co-segregated with hearing loss in the family and that it was not present in 200 unrelated control subjects with matched ancestry. This is the second report in the literature of a family with ADNSHL caused by CEACAM16 mutation. Immunofluorescence staining and western blots also prove CEACAM16 to be a secreted protein. Furthermore, our studies in transfected HEK293T cells show that the secretion efficacy of the mutant CEACAM16 is much lower than that of the wild type, suggesting a deleterious effect of the sequence variant.

Original languageEnglish (US)
Pages (from-to)119-126
Number of pages8
JournalJournal of Human Genetics
Volume60
Issue number3
DOIs
StatePublished - Mar 27 2015

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Wang, H., Wang, X., He, C., Li, H., Qing, J., Grati, M., Hu, Z., Li, J., Hu, Y., Xia, K., Mei, L., Wang, X., Yu, J., Chen, H., Jiang, L., Liu, Y., Men, M., Zhang, H., Guan, L., ... Feng, Y. (2015). Exome sequencing identifies a novel CEACAM16 mutation associated with autosomal dominant nonsyndromic hearing loss DFNA4B in a Chinese family. Journal of Human Genetics, 60(3), 119-126. https://doi.org/10.1038/jhg.2014.114