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

Wang, Honghan; Wang, Xinwei; He, Chufeng; Li, Haibo; Qi, Jie; Grati, M’hamed; Hu, Zhengmao; Li, Jia‐Da; Hu, Yuantai; Xia, Kun; Mei, Lingyun; Wang, Xingwei; Yu, Jianjun; Chen, Hongsheng; Jiang, Lu; Men, Meichao; Zhang, Hailin; Guan, Liping; Xiao, Jingjing; Zhang, Jianguo; Liu, Xuezhong

doi:10.1038/jhg.2014.114

Cited by 20 publications

(26 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The phenotypes of the 2 previously described patients with CEACAM16 variants compare well with our presented patient. The American and Chinese families are both described having binaural autosomal dominant nonsyndromic sensorineural hearing loss with an onset in the second decade of life [Zheng et al, 2011;Wang et al, 2015]. There were 2 slight differences in these families compared to our proband.…”

Section: Compatibility Of the Clinical Picturementioning

confidence: 79%

“…The audiograms currently available demonstrate stable hearing loss that will be monitored for similar progression in adulthood. Secondly, the hearing loss in the Chinese family appears in the higher frequencies, whereas the audiogram profile for our proband is flat except for 0.125 kHz [Wang et al, 2015]. A unique feature of our proband was that he exhibited noise sensitivity before the onset of his hearing loss.…”

Section: Compatibility Of the Clinical Picturementioning

confidence: 91%

“…The other variants that were also present in the sequencing dataset were communicated for the c.418A>C variant but limited to the DFNA4 region [Zheng et al, 2011]. One of the consequences of broadly screening large subsets of genes, as in the case of clinical and whole exomes, is the generation of large numbers of variants that require interpretation including synonymous variants, which could impact splice sites [Schultz et al, 2009;Wang et al, 2015]. It is common for even healthy individuals to carry private pathogenic mutations complicating the understanding of disease causing mutations [Jang et al, 2015].…”

Section: Interpretation Of the Mutation Compared To Already Detected mentioning

confidence: 99%

“…Using our described filtering parameters, these results would have been excluded as unlikely pathogenic, and we would have had difficulties in implying their pathogenicity. Both previously identified CEACAM16 mutations were detected using whole-genome linkage and whole-exome sequencing [Zheng et al, 2011;Wang et al, 2015]. The other variants that were also present in the sequencing dataset were communicated for the c.418A>C variant but limited to the DFNA4 region [Zheng et al, 2011].…”

Section: Interpretation Of the Mutation Compared To Already Detected mentioning

confidence: 99%

“…A missense mutation (c.418A>C, p.Thr140Pro) in a neighboring gene, CEACAM16 , was disclosed that led to the first association of autosomal dominant hearing loss with this gene [Zheng et al, 2011]. Recently, a Chinese family was detected with a segregating CEACAM16 missense mutation (c.505G>A, p.Gly169Arg) with a slightly different phenotype that showed increased hearing thresholds in high frequencies [Wang et al, 2015]. In this report on a German boy with postlingual hearing impairment, we provide the third missense mutation in CEACAM16 (c.1094T>G, p. Leu365Arg) and the first de novo mutation in this gene that is unanimously predicted with a likely pathogenic outcome using in silico mutation pathogenicity prediction tools.…”

mentioning

confidence: 99%

See 4 more Smart Citations

A Novel de novo Mutation in CEACAM16 Associated with Postlingual Hearing Impairment

Hofrichter¹,

Nanda²,

Gräf³

et al. 2015

Mol Syndromol

View full text Add to dashboard Cite

Mutations in CEACAM16 cause autosomal dominant nonsyndromic hearing loss (DFNA4B). So far, 2 families have been reported with segregating missense mutations, both in the immunoglobulin constant domain A of the CEACAM16 protein. In this study, we used the TruSight One panel to investigate a parent-child trio without familial history of hearing loss and one affected child. When filtering for recessive inheritance and de novo events, we discovered a de novo CEACAM16 mutation (c.1094T>G, p.Leu365Arg) as the sole likely pathogenic variant. The de novo mutation was confirmed by Sanger sequencing and STR analysis. The proband's hearing loss closely matches the described onset and severity for DFNA4B. We present the third CEACAM16 variant and the first de novo mutation in CEACAM16. This de novo mutation is robustly described as a pathogenic mutation according to in silico mutation prediction tools and affects a highly conserved amino acid in the most strongly conserved CEACAM16 N2 domain. Our strategy of screening family trios enhances de novo mutation discovery and the exclusion of other variants of potential interest through pedigree filtering.

show abstract

Section: Compatibility Of the Clinical Picturementioning

confidence: 79%

Section: Compatibility Of the Clinical Picturementioning

confidence: 91%

Section: Interpretation Of the Mutation Compared To Already Detected mentioning

confidence: 99%

Section: Interpretation Of the Mutation Compared To Already Detected mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

A Novel de novo Mutation in CEACAM16 Associated with Postlingual Hearing Impairment

Hofrichter¹,

Nanda²,

Gräf³

et al. 2015

Mol Syndromol

View full text Add to dashboard Cite

show abstract

Gene–Environment Interaction

2011

Encyclopedia of Child Behavior and Development

View full text Add to dashboard Cite

ELMOD3, a novel causative gene, associated with human autosomal dominant nonsyndromic and progressive hearing loss

Sun

Ling

et al. 2018

Hum Genet

View full text Add to dashboard Cite

Autosomal dominant nonsyndromic hearing loss (ADNSHL) is a highly genetically heterogeneous disorder. Up to date only approximately 37 ADNSHL-causing genes have been identified. The goal of this study was to determine the causative gene in a five-generation Chinese family with ADNSHL. A Chinese family was ascertained. Simultaneously, two affected individuals and one normal hearing control from the family were analyzed by whole exome capture sequencing. To assess the functional effect of the identified variant, in-vitro studies were performed. novel missense variant, c.512A>G (p.His171Arg) in exon 8 of the ELMO domain-containing 3 (ELMOD3) gene, was identified as a causative variant in this family affected by late-onset and progressive ADNSHL. The variant was validated by Sanger sequencing and found to co-segregate with the phenotype within the pedigree and was absent in 500 ethnically matched unrelated normal hearing control subjects. To our knowledge, this is the first report of a family with ADNSHL caused by ELMOD3 mutation. Western blots and immunofluorescence staining demonstrated that p.His171Arg resulted in abnormal expression levels of ELMOD3 and abnormal subcellular localization. Furthermore, the analysis of the stability of the wild-type (WT) and mutant ELMOD3 protein shows that the decay of p.His171Arg is faster than that of the WT, suggesting a shorter halflife of the c.512A > G variant. A novel variant in the ELMOD3 gene, encoding a member of the engulfment and cell motility (ELMO) family of GTPase-activating proteins, was identified for the first time as responsible for ADNSHL.

show abstract

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

Cited by 20 publications

References 37 publications

A Novel de novo Mutation in CEACAM16 Associated with Postlingual Hearing Impairment

A Novel de novo Mutation in CEACAM16 Associated with Postlingual Hearing Impairment

Gene–Environment Interaction

ELMOD3, a novel causative gene, associated with human autosomal dominant nonsyndromic and progressive hearing loss

Contact Info

Product

Resources

About