Novel recessive PDZD7 biallelic mutations associated with hereditary hearing loss in a Chinese pedigree

Abstract Background Autosomal recessive non-syndromic hearing loss (ARNSHL) is a highly heterogeneous genetic disease. PDZD7 is a new ARNSHL associated gene. Until now, nine PDZD7 biallelic mutation families with ARNSHL have been reported. Here we report a case of Chinese patient with ARNSHL linked to novel mutations in PDZD7 genes. Method The pathogenic mutations were detected by whole exome sequencing for hereditary deafness-related genes of both the proband and his parents. We used kinship detection, mutational hazard prediction, genotype-phenotype correlation analysis and variation screening for potential pathogenic mutations. Re -sequencing was used to confirm the mutations by Sanger sequence. Real time quantitative PCR (RT-qPCR) was used to analyze the PDZD7 gene expression. Population-based screening for variation frequency, evolutionary conservation comparisons, pathogenicity evaluation, and protein structure prediction were conducted to assess the pathogenicity of the novel mutations of PDZD7 gene. Results We determined three variants of the PDZD7 gene that contributed to the deafness of the patient ( PDZD7 c.192G > A, p. Met64Ile; c.1648C > T p. Gln550* and c.2341_2352delCGCAGCCGCAGCp. Arg781_Ser 784del). Pathogenic analysis in accordance with the ACMG/AMP Standards and Guidelines identified two novel mutations as Likely Pathogenic. The expression level of PDZD7 gene in the patient was decreased compared to the normal control ( P Conclusion Three mutations in PDZD7 gene linked to ARNSHL were identified in a Chinese pedigree. The findings expand not only our knowledge of genetic causes of ARNSHL, but also PDZD7 genes mutation spectrum of the disease. They will aid personalized genetic counseling, molecular diagnostics and clinical management of this condition.