Inner ear abnormalities in four patients with dRTA and SNHL: clinical and genetic heterogeneity.
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.
Andreucci
Elena
E
Department of Clinical Pathophysiology, University of Florence, Italy.
Bianchi
Benedetta
B
Carboni
Ilaria
I
Lavoratti
Giancarlo
G
Mortilla
Marzia
M
Fonda
Claudio
C
Bigozzi
Minna
M
Genuardi
Maurizio
M
Giglio
Sabrina
S
Pela
Ivana
I
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
C509766:ATP6V1B1 protein, human; C490181:ATP6V0A4 protein, human; D025262:Vacuolar Proton-Translocating ATPases; D006180:Proton-Translocating ATPases