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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2018

Open Access 01-12-2018 | Research article

Novel digenic inheritance of PCDH15 and USH1G underlies profound non-syndromic hearing impairment

Authors: Isabelle Schrauwen, Imen Chakchouk, Anushree Acharya, Khurram Liaqat, Irfanullah, Deborah A. Nickerson, Michael J. Bamshad, Khadim Shah, Wasim Ahmad, Suzanne M. Leal, University of Washington Center for Mendelian Genomics

Published in: BMC Medical Genetics | Issue 1/2018

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Abstract

Background

Digenic inheritance is the simplest model of oligenic disease. It can be observed when there is a strong epistatic interaction between two loci. For both syndromic and non-syndromic hearing impairment, several forms of digenic inheritance have been reported.

Methods

We performed exome sequencing in a Pakistani family with profound non-syndromic hereditary hearing impairment to identify the genetic cause of disease.

Results

We found that this family displays digenic inheritance for two trans heterozygous missense mutations, one in PCDH15 [p.(Arg1034His)] and another in USH1G [p.(Asp365Asn)]. Both of these genes are known to cause autosomal recessive non-syndromic hearing impairment and Usher syndrome. The protein products of PCDH15 and USH1G function together at the stereocilia tips in the hair cells and are necessary for proper mechanotransduction. Epistasis between Pcdh15 and Ush1G has been previously reported in digenic heterozygous mice. The digenic mice displayed a significant decrease in hearing compared to age-matched heterozygous animals. Until now no human examples have been reported.

Conclusions

The discovery of novel digenic inheritance mechanisms in hereditary hearing impairment will aid in understanding the interaction between defective proteins and further define inner ear function and its interactome.
Appendix
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Metadata
Title
Novel digenic inheritance of PCDH15 and USH1G underlies profound non-syndromic hearing impairment
Authors
Isabelle Schrauwen
Imen Chakchouk
Anushree Acharya
Khurram Liaqat
Irfanullah
Deborah A. Nickerson
Michael J. Bamshad
Khadim Shah
Wasim Ahmad
Suzanne M. Leal
University of Washington Center for Mendelian Genomics
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2018
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-018-0618-5

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