Hearing loss due to the mitochondrial A1555G mutation in Italian families

Abstract

Six Italian families with familial nonsyndromic hearing loss consistent with a maternal pattern of inheritance were analyzed for mitochondrial mutations. The three known mitochondrial mutations associated with nonsyndromic hearing loss were investigated by polymerase chain reaction amplification, followed by restriction fragment length analysis or DNA sequencing. The A7445G mutation and C7472 insertion were not present in either of the families, but the A1555G mutation in the 12S rRNA gene was identified in homoplasmic form in two of the families. In one of the families the onset of hearing loss is congenital, while in the other it starts later in life. The families are from different regions of Italy, and mitochondrial haplotype analysis showed that the mutation arose independently in these two families. This suggests that the A1555G mutation may not be an uncommon cause of hearing loss in Italians, and is clinically important because maternal hearing relatives of patients with the A1555G mutation are at risk for aminoglycoside induced deafness. We discuss potential reasons for the normal phenotype in some relatives with the mutation, and the different onset of hearing loss in the two families.

Nuclear and mitochondrial genes mutated in nonsyndromic impaired hearing

“…The mutation resides in a highly conserved region and has been detected in Caucasians and Asians [151][152][153]. The mutation can be found in 3% of the Japanese, and 0.5-2.4% of the European patients with SNHL [152].…”

Newborn hearing screening and genetic testing in 8974 Brazilian neonates

“…In the absence of aminoglycosides, the A1555G mutation was responsible for a clinical phenotype that ranges from severe congenital deafness to moderate progressive hearing loss with later onset, or to completely normal hearing [15,16]. Also, a Chinese family with non-syndromic hearing loss with a maternal inheritance pattern revealed in the molecular analysis the homoplasmic mtDNA mutation A827G in the MTRNR1 gene [17].…”

Mitochondrial non-syndromic sensorineural hearing loss: a clinical, audiological and pathological study from Italy, and revision of the literature

“…the hair cells of the cochlea do not replicate and consequently tend to accumulate mutant mtDNA. For this reason progressive SNHL (sensorineural hearing loss), in both its syndromic and non-syndromic forms, has been associated with a large number of mtDNA alterations [2][3][4][5][6][7][8][9][10][11][12][13][14][15]. Similarly to other mitochondrial pathologies, deafness due to mitochondrial dysfunction shows wide clinical variations.…”