title: Inner ear abnormalities in four patients with dRTA and SNHL: clinical and genetic heterogeneity.
abstract: A significant number of patients affected by autosomal recessive primary distal renal tubular acidosis (dRTA) manifest sensorineural hearing loss (SNHL). Mutations in ATP6V1B1 are associated with early onset SNHL, whereas ATP6V0A4 mutations have been described in dRTA and late-onset SNHL. Enlarged vestibular aqueduct (EVA) was described in patients with recessive dRTA and SNHL, and recently, this abnormality has been associated with mutations in the ATP6V1B1 gene. In our study, we evaluated the presence of inner-ear abnormalities in four patients affected by dRTA and SNHL, characterized by molecular analysis. Two patients affected by severe dRTA with early onset SNHL showed the same mutation in the ATP6V1B1 gene and bilateral EVA with a different degree of severity. The other two presented similar clinical manifestations of dRTA and different mutations in the ATP6V0A4 gene: one patient, showing EVA, developed an early SNHL, whereas in the other one, the SNHL appeared in the second decade of life and the vestibular aqueduct was normal. Our study confirms the association of EVA and mutations in the ATP6V1B1 gene and demonstrates that mutations in the ATP6V0A4 gene can also be associated with EVA probably only when the SNHL has an early onset. The pathophysiology of SNHL and EVA are still to be defined.
authors.affiliation: Department of Clinical Pathophysiology, University of Florence, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Andreucci
authors.forename: Benedetta
authors.initials: B
authors.lastname: Bianchi
authors.forename: Ilaria
authors.initials: I
authors.lastname: Carboni
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Lavoratti
authors.forename: Marzia
authors.initials: M
authors.lastname: Mortilla
authors.forename: Claudio
authors.initials: C
authors.lastname: Fonda
authors.forename: Minna
authors.initials: M
authors.lastname: Bigozzi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Genuardi
authors.forename: Sabrina
authors.initials: S
authors.lastname: Giglio
authors.forename: Ivana
authors.initials: I
authors.lastname: Pela
mesh_terms: D000141:Acidosis, Renal Tubular / Q000150:complications / Q000235:genetics*; D007758:Ear, Inner / Q000002:abnormalities* / Q000000981:diagnostic imaging; D005260:Female; D005808:Genes, Recessive; D018740:Genetic Heterogeneity; D006319:Hearing Loss, Sensorineural / Q000150:complications / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D006180:Proton-Translocating ATPases / Q000235:genetics; D011859:Radiography; D012720:Severity of Illness Index; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics; D014723:Vestibular Aqueduct / Q000002:abnormalities / Q000000981:diagnostic imaging
chemical_list: C509766:ATP6V1B1 protein, human; C490181:ATP6V0A4 protein, human; D025262:Vacuolar Proton-Translocating ATPases; D006180:Proton-Translocating ATPases