title: Digenic mutations involving both the BSND and GJB2 genes detected in Bartter syndrome type IV.
abstract: 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.
authors.affiliation: Department of Head and Neck Surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410013, China.
authors.forename: Hong-Han
authors.initials: HH
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology, Head & Neck Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; State Key Laboratory of Medical Genetics, Changsha, 410078, Hunan, China; Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, 410008, Hunan, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Ophtalmology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Li
authors.affiliation: Department of Otolaryngology, Head & Neck Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Otolaryngology, Head & Neck Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
authors.forename: Ling-Yun
authors.initials: LY
authors.lastname: Mei
authors.affiliation: Department of Otolaryngology, Head & Neck Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
authors.forename: Xing-Wei
authors.initials: XW
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology, Head & Neck Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Otolaryngology, Head & Neck Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China. Electronic address: hechufeng2013@163.com.
authors.forename: Chu-Feng
authors.initials: CF
authors.lastname: He
mesh_terms: D001477:Bartter Syndrome / Q000150:complications / Q000235:genetics*; D002675:Child, Preschool; D018118:Chloride Channels / Q000235:genetics*; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D005091:Exons; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009154:Mutation
chemical_list: C440005:BSND protein, human; D018118:Chloride Channels; D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26
keywords: BSND; Bartter syndrome; Digenic mutations; GJB2; Sensorineural deafness