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

@article{Hofrichter2015AND,
  title={A Novel de novo Mutation in CEACAM16 Associated with Postlingual Hearing Impairment},
  author={Michaela A. H. Hofrichter and Indrajit Nanda and Jens Gr{\"a}f and J{\"o}rg Schr{\"o}der and Wafaa Shehata-Dieler and Barbara Vona and Thomas Haaf},
  journal={Molecular Syndromology},
  year={2015},
  volume={6},
  pages={156 - 163}
}
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… 

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References

SHOWING 1-10 OF 39 REFERENCES

Exome Sequencing Identifies a Novel CEACAM16 Mutation Associated with Autosomal Dominant Nonsyndromic Hearing Loss DFNA4B in a Chinese Family

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 and identified a heterozygous missense mutation in exon 3 of the CEACAM16 gene, suggesting a deleterious effect of the sequence variant.

Mutations of the gene encoding otogelin are a cause of autosomal-recessive nonsyndromic moderate hearing impairment.

An alpha-tectorin gene defect causes a newly identified autosomal recessive form of sensorineural pre-lingual non-syndromic deafness, DFNB21.

Comparison of the phenotype of the DFNB21 heterozygous carriers with that of DFNA8/12-affected individuals supports the hypothesis that the TECTA mutations which cause the dominant form of deafness have a dominant-negative effect, and provides genetic evidence for alpha-tectorin forming homo- or heteromeric structures.

A framework for the interpretation of de novo mutation in human disease

This model is used to identify ∼1,000 genes that are significantly lacking in functional coding variation in non-ASD samples and are enriched for de novo loss-of-function mutations identified in ASD cases, suggesting that the role of de noVO mutations in ASDs might reside in fundamental neurodevelopmental processes.

Mutations in OTOGL, encoding the inner ear protein otogelin-like, cause moderate sensorineural hearing loss.

Identification of CRYM as a candidate responsible for nonsyndromic deafness, through cDNA microarray analysis of human cochlear and vestibular tissues.

The results strongly implicate CRYM in normal auditory function and identify it as one of the genes that can be responsible for nonsyndromic deafness.

De novo mutations in human genetic disease

Recent findings suggesting that de novo mutations play a prominent part in rare and common forms of neurodevelopmental diseases, including intellectual disability, autism and schizophrenia are discussed.

Mutations in the human alpha-tectorin gene cause autosomal dominant non-syndromic hearing impairment.

The findings indicate that mutations in TECTA are responsible for hearing impairment in these families, and implicate a new type of protein in the pathogenesis of hearing impairment.

Mutations in the human α-tectorin gene cause autosomal dominant non-syndromic hearing impairment

The findings indicate that mutations in TECTA are responsible for hearing impairment in these families, and implicate a new type of protein in the pathogenesis of hearing impairment.