Mutation in PCDH15 may modify the phenotypic expression of the 7511T>C mutation in MT-TS1 in a Chinese Han family with maternally inherited nonsyndromic hearing loss

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• 作者：Dong-ye Chen^a ; ^b ; ^c ; ¹ ; Wei-dong Zhu^a ; ^b ; ^c ; ¹ ; Yong-chuan Chai^a ; ^b ; ^c ; Ying Chen^a ; ^b ; ^c ; Lianhua Sun^a ; ^b ; ^c ; Tao Yang^a ; ^b ; ^c ; ^{yangtfxl@sina.com" class="auth_mail" title="E-mail the corresponding author} ; Hao Wu^a ; ^b ; ^c ; ^{wuhao622@sina.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Hearing loss ; Mitochondria ; Mutation ; Modifier
• 刊名：International Journal of Pediatric Otorhinolaryngology
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：79
• 期：10
• 页码：1654-1657
• 全文大小：709 K

文摘

Mutations in MT-TS1 have been found to be associated with nonsyndromic sensorineural hearing loss (SNHL). PCDH15 codes for protocadherin-15, a member of the cadherin superfamily of calcium-dependent cell-cell adhesion molecules. In this study, we analyzed the correlation of both MT-TS1 and PCDH15 mutations in a Chinese Han family segregating maternally inherited nonsyndromic SNHL.

Methods

We ascertained a Chinese Han family segregating maternally inherited nonsyndromic sensorineural hearing loss. Eight of 10 maternal members in this family exhibited late-onset, progressive hearing impairment. Mutation screening of 79 known deafness genes was performed for the proband by targeted next-generation sequencing.

Results

15">A total of 651 variants were detected in this individual. Among them, a homoplasmic 7511T>C variant in MT-TS1, the mitochondrial tRNA ^Ser(UCN) gene, and a heterozygous p.Asp1010Gly variant in PCDH15 were more likely to be pathogenic. Consistent with the matrilineal inheritance with reduced penetrance, the 7511T>C variant in MT-TS1 was found in all 10 maternal members and an additional heterozygous p.Asp1010Gly variant in PCDH15 cosegregated with the hearing loss in this family.

Conclusion

Our results suggested that the PCDH15 p.Asp1010Gly variant probably modified the phenotypic expression of the 7511T>C mutation in MT-TS1.