GJB2 and GJB6 genes: molecular study and identification of novel GJB2 mutations in the hearing impaired Argentinean population

DALAMÓN V; LOTERSZTEIN V; BEHERAN A; LIPOVSEK M; DIAMANTE F; PALLARES N; FRANCIPANE L; FRECHTEL G; PAOLI B; MANSILLA E; DIAMANTE V; ELGOYHEN AB

AUDIOLOGY AND NEURO-OTOLOGY

KARGER

Año: 2010 vol. 15 p. 194 - 202

1420-3030

Mutations in the GJB2 gene are responsible for more than half of all cases of prelingual, recessive, inherited, non-syndromic deafness in Europe. This paper presents a mutation analysis of the GJB2, GJB6, OTOF and MTRNR1 genes in 252 Argentinean patients with sensorineural non-syndromic hearing loss (61 familial and 191 non-familial cases). Thirty one different mutations were identified in GJB2 and GJB6 in 86 of the 252 (34%) patients. Previously reported mutations found were: IVS+1G>A, T8M, G12V, c.35delG, V27I, M34T, V37I, E47X, 167delT, R75W, W77R, I82M, F83L, L90P, c.269insT, V95M, c.333delAA, R127H, E129K, R143W, V153I, G160S, M163L, M163V, R184P, K168R, 682C>T, del(GJB6-D13S1830), del(GJB6-D13S1854). In addition, we describe for the first time two new mutations in GJB2: the missense mutation c.29 T>C producing the change of proline for leucine (L10P) in the N terminal domain and c.326 G>T, which leads to a valine for glycine (G109V) substitution in the intracytoplasmatic domain. Mutation Q829X in OTOF and A15556 in MTRNR1 were not found in our cohort. This work shows the high prevalence of GJB2 mutations in the Argentinean population, with frequencies that are comparable to those of the Mediterranean area. Most importantly, it adds two novel GJB2 mutations to be taken in consideration in the genetic diagnosis of sensorineural non-syndromic hearing loss.