Modifier factors influencing the phenotypic manifestation of the deafness associated mitochondrial DNA mutations / 中华医学遗传学杂志
Chinese Journal of Medical Genetics
;
(6): 165-171, 2011.
Artigo
em Chinês
| WPRIM
| ID: wpr-326971
ABSTRACT
Mutations in the mitochondrial DNA have been found to be one of the most important causes of sensorineural hearing loss. In particular, these mutations often occur in the mitochondrial 12S rRNA and tRNA genes. Of these, the homoplasmic A1555G and C1494T mutations in the 12S rRNA have been associated with both aminoglycoside induced and nonsyndromic hearing impairment in many families worldwide. Children carrying the A1555G or C1494T mutation are susceptible to the exposure of ototoxic drugs, thereby inducing or worsening hearing loss. Individuals harboring A1555G or C1494T mutation can also develop hearing loss even in the absence of aminoglycoside exposure. However, matrilineal relatives of intra-families or inter-families carrying the A1555G or C1494T mutation exhibit a wide range of severity, age-at-onset, and audiometric configuration of hearing impairment. These indicate that the A1555G or C1494T mutation is a primary factor underlying the development of deafness but insufficient to produce the clinical phenotype.Thus, other modifier factors, such as aminoglycoside(s), mitochondria l DNA haplotype(s) or nuclear modifier gene(s), play a role in the phenotypic expression of the deafness-associated mitochondrial 12S rRNA A1555G or C1494T mutation. In this review, we summarize the modifier factors for the phenotypic expression of deafness-associated 12S rRNA A1555G and C1494T mutations and propose the molecular pathogenetic mechanism of maternally inherited deafness.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fenótipo
/
DNA Mitocondrial
/
Dados de Sequência Molecular
/
Sequência de Bases
/
Surdez
/
Genética
/
Perda Auditiva Neurossensorial
/
Mutação
Limite:
Humanos
Idioma:
Chinês
Revista:
Chinese Journal of Medical Genetics
Ano de publicação:
2011
Tipo de documento:
Artigo
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