title: Genetic investigation of autosomal recessive distal renal tubular acidosis: evidence for early sensorineural hearing loss associated with mutations in the ATP6V0A4 gene.
abstract: Mutations in the ATP6V1B1 and ATP6V0A4 genes, encoding subunits B1 and 4 of apical H(+) ATPase, cause recessive forms of distal renal tubular acidosis (dRTA). ATP6V1B mutations have been associated with early sensorineural hearing loss (SNHL), whereas ATP6V0A4 mutations are classically associated with either late-onset SNHL or normal hearing. The phenotype and genotype of 39 new kindreds with recessive dRTA, 18 of whom were consanguineous, were assessed. Novel and known loss-of-function mutations were identified in 31 kindreds. Fourteen new and five recurrent mutations of the ATP6V0A4 gene were identified in 21 families. For the ATP6V1B1 gene, two new and two previously described mutations were identified in 10 families. Surprisingly, seven probands with ATP6V0A4 gene mutations developed severe early SNHL between the ages of 2 mo and 10 yr. No mutation was detected in eight families. These data extend the spectrum of disease-causing mutations and provide evidence for genetic heterogeneity in SNHL. The data also demonstrate that mutations in either of these genes may cause early deafness, and they highlight the importance of genetic screening for recessive forms of dRTA independent of hearing status.
authors.affiliation: Centre Hospitalier Universitaire de Rouen, Département de Pédiatrie Médicale, and Faculté de Médecine et de Pharmacie, Rouen, France. rosa.vargas-poussou@chu-rouen.fr
authors.forename: Rosa
authors.initials: R
authors.lastname: Vargas-Poussou
authors.forename: Pascal
authors.initials: P
authors.lastname: Houillier
authors.forename: Nelly
authors.initials: N
authors.lastname: Le Pottier
authors.forename: Laurence
authors.initials: L
authors.lastname: Strompf
authors.forename: Chantal
authors.initials: C
authors.lastname: Loirat
authors.forename: Véronique
authors.initials: V
authors.lastname: Baudouin
authors.forename: Marie-Alice
authors.initials: MA
authors.lastname: Macher
authors.forename: Michèle
authors.initials: M
authors.lastname: Déchaux
authors.forename: Tim
authors.initials: T
authors.lastname: Ulinski
authors.forename: François
authors.initials: F
authors.lastname: Nobili
authors.forename: Philippe
authors.initials: P
authors.lastname: Eckart
authors.forename: Robert
authors.initials: R
authors.lastname: Novo
authors.forename: Mathilde
authors.initials: M
authors.lastname: Cailliez
authors.forename: Rémi
authors.initials: R
authors.lastname: Salomon
authors.forename: Hubert
authors.initials: H
authors.lastname: Nivet
authors.forename: Pierre
authors.initials: P
authors.lastname: Cochat
authors.forename: Ivan
authors.initials: I
authors.lastname: Tack
authors.forename: Anne
authors.initials: A
authors.lastname: Fargeot
authors.forename: François
authors.initials: F
authors.lastname: Bouissou
authors.forename: Gwenaelle Roussey
authors.initials: GR
authors.lastname: Kesler
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Lorotte
authors.forename: Nathalie
authors.initials: N
authors.lastname: Godefroid
authors.forename: Valérie
authors.initials: V
authors.lastname: Layet
authors.forename: Gilles
authors.initials: G
authors.lastname: Morin
authors.forename: Xavier
authors.initials: X
authors.lastname: Jeunemaître
authors.forename: Anne
authors.initials: A
authors.lastname: Blanchard
mesh_terms: D000141:Acidosis, Renal Tubular / Q000453:epidemiology* / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D025063:Chromosome Disorders / Q000453:epidemiology / Q000235:genetics; D002874:Chromosome Mapping; D015897:Comorbidity; D004252:DNA Mutational Analysis; D019317:Evidence-Based Medicine; D005260:Female; D005602:France / Q000453:epidemiology; D005808:Genes, Recessive / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D006319:Hearing Loss, Sensorineural / Q000453:epidemiology* / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D007223:Infant; D015810:Linkage Disequilibrium; D008297:Male; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics*; D009154:Mutation; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors
chemical_list: C501005:MT-ATP6 protein, human; D025261:Mitochondrial Proton-Translocating ATPases