Article Text

Download PDFPDF
Short report
A mutation of MET, encoding hepatocyte growth factor receptor, is associated with human DFNB97 hearing loss
  1. Ghulam Mujtaba1,
  2. Julie M Schultz2,3,
  3. Ayesha Imtiaz1,
  4. Robert J Morell2,
  5. Thomas B Friedman2,
  6. Sadaf Naz1
  1. 1School of Biological Sciences, University of the Punjab, Lahore, Pakistan
  2. 2Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, USA
  3. 3Present address, GeneDx, Gaithersburg, Maryland, USA
  1. Correspondence to Dr Sadaf Naz, School of Biological Sciences, University of the Punjab, Lahore 54590, Pakistan; naz.sbs{at}pu.edu.pk

Abstract

Background Hearing loss is a heterogeneous neurosensory disorder. Mutations of 56 genes are reported to cause recessively inherited non-syndromic deafness.

Objective We sought to identify the genetic lesion causing hearing loss segregating in a large consanguineous Pakistani family.

Methods and results Mutations of GJB2 and all other genes reported to underlie recessive deafness were ruled out as the cause of the phenotype in the affected members of the participating family. Homozygosity mapping with a dense array of one million SNP markers allowed us to map the gene for recessively inherited severe hearing loss to chromosome 7q31.2, defining a new deafness locus designated DFNB97 (maximum logarithm of the odds score of 4.8). Whole-exome sequencing revealed a novel missense mutation c.2521T>G (p.F841V) in MET (mesenchymal epithelial transition factor), which encodes the receptor for hepatocyte growth factor. The mutation cosegregated with the hearing loss phenotype in the family and was absent from 800 chromosomes of ethnically matched control individuals as well as from 136 602 chromosomes in public databases of nucleotide variants. Analyses by multiple prediction programmes indicated that p.F841V likely damages MET function.

Conclusions We identified a missense mutation of MET, encoding the hepatocyte growth factor receptor, as a likely cause of hearing loss in humans.

  • Genetics
  • Genome-wide
  • Linkage
  • Molecular genetics

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.