title: Exome sequencing identifies a novel CEACAM16 mutation associated with autosomal dominant nonsyndromic hearing loss DFNA4B in a Chinese family.
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.
authors.affiliation: Department of Otolaryngology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, China.|Department of Head and Neck Surgery, Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan, China.|Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, Hunan, China.
authors.forename: Honghan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, China.|Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, Hunan, China.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, China.|Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, Hunan, China.
authors.forename: Chufeng
authors.initials: C
authors.lastname: He
authors.affiliation: State Key Laboratory of Medical Genetics of China, Changsha, Hunan, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Otorhinolaryngology, University of Miami, Miller School of Medicine, Miami, FL, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Qing
authors.affiliation: Department of Otorhinolaryngology, University of Miami, Miller School of Medicine, Miami, FL, USA.
authors.forename: Mhamed
authors.initials: M
authors.lastname: Grati
authors.affiliation: State Key Laboratory of Medical Genetics of China, Changsha, Hunan, China.
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Medical Genetics of China, Changsha, Hunan, China.
authors.forename: Jiada
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Genetics of China, Changsha, Hunan, China.
authors.forename: Yiqiao
authors.initials: Y
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Medical Genetics of China, Changsha, Hunan, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.affiliation: Department of Otolaryngology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, China.|Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, Hunan, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Mei
authors.affiliation: Department of Otolaryngology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, China.|Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, Hunan, China.
authors.forename: Xingwei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Head and Neck Surgery, Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Otolaryngology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, China.|Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, Hunan, China.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, China.|Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, Hunan, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Otolaryngology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, China.|Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, Hunan, China.
authors.forename: Yalan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, China.|Health Management Center, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Meichao
authors.initials: M
authors.lastname: Men
authors.affiliation: Department of Head and Neck Surgery, Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan, China.
authors.forename: Hailin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: BGI-Shenzhen, Shenzhen, Guangdong, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Guan
authors.affiliation: BGI-Shenzhen, Shenzhen, Guangdong, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Xiao
authors.affiliation: BGI-Shenzhen, Shenzhen, Guangdong, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Otorhinolaryngology, University of Miami, Miller School of Medicine, Miami, FL, USA.
authors.forename: Xuezhong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, China.|State Key Laboratory of Medical Genetics of China, Changsha, Hunan, China.|Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, Hunan, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Feng
mesh_terms: D000328:Adult; D000818:Animals; D044466:Asian People / Q000208:ethnology; D015153:Blotting, Western; D019556:COS Cells; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D002681:China; D003638:Deafness / Q000208:ethnology / Q000235:genetics / Q000473:pathology; D059472:Exome / Q000235:genetics*; D005192:Family Health; D005260:Female; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D057809:HEK293 Cells; D006319:Hearing Loss, Sensorineural / Q000208:ethnology / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA / Q000379:methods*; D055815:Young Adult
chemical_list: D015815:Cell Adhesion Molecules; C558358:CEACAM16 protein, human