Whole Exon Sequencing Combined with Copy Number Variation Detection for Hereditary Deafness

ZHANG Yuanhui; LIN Ying; CHEN Yiwen; LIU Xiaoping; YU Feng

doi:10.3969/j.issn.1672-2922.2024.01.019

Abstract：Objective To determine the value of whole exon sequencing(WES)combined with copy number vari-ation(CNV)detection in diagnosis of hereditary deafness,and to further understanding of CNV.Methods A child with binaural moderate sensorineural hearing loss without a family history of genetic disorders or a history of ototoxic medi-cation was admitted to our department.Endoscopy,imaging,subjective and objective audiologic examinations were completed.Peripheral blood samples were collected,and WES was performed to identify the cause of the child's deaf-ness,with the target sequence confirmed by multiple ligation-dependent probe amplification(MLPA).Results Audio-metric,ABR and ASSR thresholds indicated moderate sensorineural deafness.WES showed 12 homozygous variants lo-cated in chromosomes 1(CR1 gene,splice-20),5(ZSWIM6 gene and SMN1 gene,coding-synon),and 6(ATXN1 gene,cds-del;TENT5A,cds-ins),7(CFTR gene,intron),8(TG,promoter),9(PRDM12 gene,cds-del),10(TUBGCP2 gene,splice+20),11(TENM4 gene,splice+20),15(STRC gene,deletion)and 16(ABCC11 gene,missense).Based on ACMG guidelines and comprehensive history analysis,only the STRC gene variant(NM_153700.2:EX1-EX29E Del)was deter-mined to be pathogenic,while the rest variants were considered benign or potentially benign.The target sequence was verified by MLPA.Conclusion Deletion of DFNB16(OMIM:603720)in the STRC gene caused bilateral moderate sen-sorineural deafness in this case.In the clinic,a wide range of detection techniques at various levels can be selected for diagnosis purposes based on the patient's medical history.Such knowledge can enhance the understanding of CNV and its relations to hereditary deafness among otologists.