Journal of Shandong University (Health Sciences) ›› 2022, Vol. 60 ›› Issue (1): 27-33.doi: 10.6040/j.issn.1671-7554.0.2021.0363

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Novel pathogenic gene variants in a pedigree with nonsyndromic hearing loss

LI Xingxing1, ZHOU Yongan2, LI Zhe1, BAI Yuan1   

  1. 1. Graduate School, Shanxi Medical University, Taiyuan 030001, Shanxi, China;
    2. Department of Blood Transfusion, Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, China
  • Published:2022-01-08

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Abstract: Objective To explore the genetic basis of a pedigree with nonsyndromic hearing loss(NSHL). Methods Peripheral blood samples of all family members were collected and whole-exome sequencing(WES)technique was performed in four members. Then Sanger sequencing was performed in all members to identify the genetic cause of the disease and pathogenicity was detected with cytology. Results All patients in this pedigree carried PCDH15c.4765delC(p.Leu1589Serfs*13)and CDH23c.9617G>A(p.Arg3206His)heterozygous variants, while other members carried PCDH15c.4765delC(p.Leu1589Serfs*13)or CDH23c.9617G>A(p.Arg3206His)single heterozygous variant, of which PCDH15c.4765delC was an unreported new variant. The frame shift mutation of PCDH15 gene caused a truncated protein and its expression decreased significantly. Immunofluorescence showed that mutant proteins accumulated in cytoplasm, which might be caused by the gene variant. Conclusion The PCDH15c.4765delC(p.Leu1589Serfs*13)and CDH23c.9617G>A(p.Arg3206His)digenic variants may cause the NSHL in the pedigree. The detection of new variant enriches the variants spectrum of deafness-causing genes and enables genetic counseling and prenatal diagnosis of the family.

Key words: Nonsyndromic hearing loss, Digenic heterozygous variants, PCDH15 gene, CDH23 gene

CLC Number: 

  • R764.43
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