A novel P2RX2 mutation in an Italian family affected by autosomal dominant nonsyndromic hearing loss

Flavio Faletra, Giorgia Girotto, Adamo Pio D'Adamo, Diego Vozzi, Anna Morgan, Paolo Gasparini

Research output: Contribution to journalArticlepeer-review


Hereditary hearing loss (HHL) is a common disorder accounting for at least 60% of prelingual deafness. It is characterized by a large genetic heterogeneity, and despite the presence of a major gene, still there is a need to search for new causative mutations/genes. Very recently, a mutation within ATP-gated P2X(2) receptor (ligand-gated ion channel, purinergic receptor 2) gene (P2RX2) at DNFA41 locus has been reported leading to a bilateral and symmetrical sensorineural non-syndromic autosomal dominant HHL in two Chinese families. We performed a linkage analysis in a large Italian family with a dominant pattern of inheritance showing a significant 3.31 LOD score in a 2. Mb region overlapping with the DNFA41 locus. Molecular analyses of P2RX2 identified a novel missense mutation (p.Gly353Arg) affecting a residue highly conserved across species. Visual inspection of the protein structure as obtained from comparative modeling suggests that substitution of the small glycine residue with a charged bulky residue such as an arginine that is close to the 'neck' of the region responsible for ion channel gating should have a high energetic cost and should lead to a severely destabilization of the fold. The identification of a second most likely causative mutation in P2RX2 gene further supports the possible role of this gene in causing autosomal dominant HHL.

Original languageEnglish
Pages (from-to)236-239
Number of pages4
Issue number2
Publication statusPublished - Jan 25 2014


  • DFNA41
  • Mutation
  • P.Gly353Arg
  • P2RX2

ASJC Scopus subject areas

  • Genetics


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