Novel recessive PDZD7 biallelic mutations in two Chinese families with non-syndromic hearing loss

Am J Med Genet A. 2018 Jan;176(1):99-106. doi: 10.1002/ajmg.a.38477. Epub 2017 Oct 19.


Autosomal recessive non-syndromic hearing loss (ARNSHL) is a highly heterogeneous genetic condition. PDZD7 has emerged as a new genetic etiology of ARNSHL. Biallelic mutations in the PDZD7 gene have been reported in two German families, four Iranian families, and a Pakistani family with ARNSHL. The effect of PDZD7 on ARNSHL in other population has yet to be elucidated. Two Chinese ARNSHL families, each of which had two affected siblings, were included in this study. The families underwent target region capture and high-throughput sequencing to analyze the exonic, splice-site, and intronic sequences of 128 genes. Furthermore, 1751 normal Chinese individuals served as controls, and 122 Chinese families segregating with apparent ARNSHL, who had been previously excluded for variants in the common deafness genes GJB2 and SLC26A4, were subjected to screening for candidate mutations. We identified a novel homozygous missense mutation (p.Arg66Leu) and novel compound heterozygous frameshift mutations (p.Arg56fsTer24 and p.His403fsTer36) in Chinese families with ARNSHL. This is the first report to identify PDZD7 as an ARNSHL-associated gene in the Chinese population. Our finding could expand the pathogenic spectrum and strengthens the clinical diagnostic role of the PDZD7 gene in ARNSHL patients.

Keywords: PDZD7; biallelic mutation; deafness; non-syndromic hearing loss.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Computational Biology / methods
  • DNA Mutational Analysis
  • Female
  • Genes, Recessive*
  • Genetic Association Studies*
  • Genomics / methods
  • Hearing Loss / diagnosis*
  • Hearing Loss / genetics*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Models, Molecular
  • Mutation*
  • Pedigree
  • Protein Conformation
  • Structure-Activity Relationship


  • Carrier Proteins
  • PDZD7 protein, human