title: Mutation analysis and audiologic assessment in six Chinese children with primary distal renal tubular acidosis.
abstract: The objective of this study is to identify ATP6V1B1, ATP6V0A4 and SLC4A1 genes mutations and assess audiologic characteristics in six Chinese children with primary distal renal tubular acidosis from four unrelated families between the ages of 2 and 13 years. Both ATP6V0A4 and ATP6V1B1 genes were preferentially screened in all index cases by direct sequence analysis. If inconclusive then SLC4A1 gene should be analyzed for mutation. Their clinical features, hearing status and inner ear imaging structure were also investigated. Six loss-of-function mutations were identified in six patients. Two novel mutations were identified in either of ATP6V0A4 and ATP6V1B1 genes, respectively. Two probands from different kindreds with mutations in ATP6V1B1 presented early onset profound sensorineural hearing loss (SNHL) and enlarged vestibular aqueduct (EVA). Two from different families carrying ATP6V0A4 mutations manifested early onset moderate mixed HL and moderate SNHL, respectively, the former comorbid with EVA, while the latter not; however, both their elder sisters showed normal hearing and inner ear. These findings expand the spectrum of mutations in the ATP6V0A4 and ATP6V1B1 genes associated with primary dRTA. Our study confirms the association of EVA and mutations in either of these two genes. More studies are necessary to clarify the relationship between dRTA, SNHL, EVA, and gene mutations.
authors: Department of Nephrology, The Affiliated Hospital of Medical College Qingdao University , Qingdao , P.R. China .
authors: Yanxia
authors: Y
authors: Gao
authors: Yan
authors: Y
authors: Xu
authors: Qingyang
authors: Q
authors: Li
authors: Yanhua
authors: Y
authors: Lang
authors: Qian
authors: Q
authors: Dong
authors: Leping
authors: L
authors: Shao
mesh_terms: D000141:Acidosis, Renal Tubular / Q000150:complications* / Q000235:genetics*; D000293:Adolescent; D001457:Anion Exchange Protein 1, Erythrocyte / Q000235:genetics*; D044466:Asian People; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000150:complications* / Q000235:genetics*; D006320:Hearing Tests; D006801:Humans; D008297:Male; D009154:Mutation; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics*
chemical_list: C509766:ATP6V1B1 protein, human; D001457:Anion Exchange Protein 1, Erythrocyte; C454201:SLC4A1 protein, human; C490181:ATP6V0A4 protein, human; D025262:Vacuolar Proton-Translocating ATPases
keywords: ATP6V0A4 gene, ATP6V1B1 gene; Distal renal tubular acidosis; enlarged vestibular aqueduct; gene mutation; hearing loss