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Exome sequencing identifies a novel CEACAM16 mutation associated with autosomal dominant nonsyndromic hearing loss DFNA4B in a Chinese family.
- Source :
-
Journal of human genetics [J Hum Genet] 2015 Mar; Vol. 60 (3), pp. 119-126. Date of Electronic Publication: 2015 Jan 15. - Publication Year :
- 2015
-
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.
- Subjects :
- Adult
Animals
Asian People ethnology
Blotting, Western
COS Cells
Cell Adhesion Molecules metabolism
China
Deafness ethnology
Deafness genetics
Deafness pathology
Family Health
Female
Genes, Dominant
Genotype
HEK293 Cells
Hearing Loss, Sensorineural ethnology
Hearing Loss, Sensorineural genetics
Hearing Loss, Sensorineural pathology
Humans
Male
Microscopy, Confocal
Middle Aged
Pedigree
Polymorphism, Single Nucleotide
Young Adult
Cell Adhesion Molecules genetics
Exome genetics
Genetic Predisposition to Disease genetics
Mutation, Missense
Sequence Analysis, DNA methods
Subjects
Details
- Language :
- English
- ISSN :
- 1435-232X
- Volume :
- 60
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of human genetics
- Publication Type :
- Academic Journal
- Accession number :
- 25589040
- Full Text :
- https://doi.org/10.1038/jhg.2014.114