Digenic mutations involving both the BSND and GJB2 genes detected in Bartter syndrome type IV

详细信息    查看全文

• 作者：Hong-han Wang^a ; Yong Feng^b ; ^c ; ^d ; Hai-bo Li^e ; Hong Wu^b ; Ling-yun Mei^b ; Xing-wei Wang^b ; Lu Jiang^b ; Chu-feng He^b ; ^{hechufeng2013@163.com}
• 关键词：Bartter syndrome ; Sensorineural deafness ; BSND ; GJB2 ; Digenic mutations
• 刊名：International Journal of Pediatric Otorhinolaryngology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：92
• 期：Complete
• 页码：17-20
• 全文大小：818 K
• 卷排序：92

文摘

Bartter syndrome type IV, characterized by salt-losing nephropathies and sensorineural deafness, is caused by mutations of BSND or simultaneous mutations of both CLCNKA and CLCNKB. GJB2 is the primary causative gene for non-syndromic sensorineural deafness and associated with several syndromic sensorineural deafness. Owing to the rarity of Bartter syndrome, only a few mutations have been reported in the abovementioned causative genes. To investigate the underlying mutations in a Chinese patient with Bartter syndrome type IV, genetic analysis of BSND, CLCNKA, CLCNKB and GJB2 were performed by polymerase chain reaction and direct sequencing. Finally, double homozygous mutations c.22C > T (p.Arg8Trp) and c.127G > A (Val43Ile) were detected in exon 1 of BSND. Intriguingly, compound heterozygous mutations c.235delC (p.Leu79CysfsX3) and c.109G > A (p.Val37Ile) were also revealed in exon 2 of GJB2 in the same patient. No pathogenic mutations were found in CLCNKA and CLCNKB. Our results indicated that the homozygous mutation c.22C > T was the key genetic reason for the proband, and a digenic effect of BSND and GJB2 might contributed to sensorineural deafness. To our knowledge, it was the first report showing that the GJB2 gene mutations were detected in Bartter syndrome.