Mitochondrial DNA A1555G mutation screening using a testing kit method and its significance in preventing aminoglycoside-related hearing loss

To elucidate the pathophysiological and genetic mechanisms of hearing loss associated with the homoplasmic mitochondrial A1555G mutation in the absence of aminoglycoside exposure, we conducted audiological and genetic analyses on 67 maternally related members of a large Japanese family carrying this mutation. A consistent pattern was evident in the audiograms, with features of sensory presbycusis, cochlear origin at all levels of hearing loss, and a high degree of vulnerability of outer hair cells. That the degree of hearing loss was similar in affected subjects within the same sibling group but differed between sibling groups suggests the involvement of nuclear modifier genes. Total mitochondrial DNA sequences were completely identical among subjects with various levels of hearing loss, and lacked additional pathogenic mutations. For the diagnosis of sensorineural hearing loss, the mitochondrial A1555G mutation should be considered when these features are present even in the absence of aminoglycoside exposure.

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Phylogenetic analysis of mitochondrial DNA in Japanese pedigrees of sensorineural hearing loss associated with the A1555G mutation

European Journal of Human Genetics ◽

10.1038/sj.ejhg.5200239 ◽

1998 ◽

Vol 6 (6) ◽

pp. 563-569 ◽

Cited By ~ 18

Author(s):

Satoko Abe ◽

Shin-ichi Usami ◽

Hideichi Shinkawa ◽

MikeD Weston ◽

LarryD Overbeck ◽

...

Keyword(s):

Phylogenetic Analysis ◽

Hearing Loss ◽

Mitochondrial Dna ◽

Sensorineural Hearing Loss ◽

Sensorineural Hearing ◽

A1555g Mutation

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

Bioscience Reports ◽

10.1042/bsr20070027 ◽

2008 ◽

Vol 28 (1) ◽

pp. 49-59 ◽

Cited By ~ 23

Author(s):

Stefano Berrettini ◽

Francesca Forli ◽

Susanna Passetti ◽

Anna Rocchi ◽

Luca Pollina ◽

...

Keyword(s):

Hearing Loss ◽

Mitochondrial Dna ◽

Sensorineural Hearing Loss ◽

Hearing Impairment ◽

Sensorineural Hearing ◽

Pathological Study ◽

Mtdna Mutations ◽

A1555g Mutation ◽

Sensorineural Hearing Impairment

Over the last decade, a number of distinct mutations in the mtDNA (mitochondrial DNA) have been found to be associated with both syndromic and non-syndromic forms of hearing impairment. Their real incidence as a cause of deafness is poorly understood and generally underestimated. Among the known mtDNA mutations, the A1555G mutation in the 12S gene has been identified to be one of the most common genetic cause of deafness, and it has been described to be both associated to non-syndromic progressive SNHL (sensorineural hearing loss) and to aminoglycoside-induced SNHL. In the present study, we have investigated the presence of mtDNA alterations in patients affected by idiopathic non-syndromic SNHL, both familiar and sporadic, in order to evaluate the frequency of mtDNA alterations as a cause of deafness and to describe the audiological manifestations of mitochondrial non-syndromic SNHL. In agreement with previous studies, we found the A1555G mutation to be responsible for a relevant percentage (5.4%) of cases affected with isolated idiopathic sensorineural hearing impairment.

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