Maternally inherited aminoglycoside-induced and nonsyndromic hearing loss in five Han Chinese pedigrees / 中华医学遗传学杂志
Chinese Journal of Medical Genetics
; (6): 367-373, 2011.
Article
en Zh
| WPRIM
| ID: wpr-326931
Biblioteca responsable:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To study the effect of the mitochondrial 12S rRNA mutations on aminoglycoside-induced and nonsyndromic hearing loss, to carry out the clinical and molecular characterization of five Han Chinese pedigrees with maternally transmitted aminoglycoside-induced and nonsyndromic hearing loss.</p><p><b>METHODS</b>Five pedigrees of maternally transmitted aminoglycoside-induced and nonsyndromic hearing loss were collected, genomic DNA was extracted, and complete mitochondrial genomes and the gap junction protein beta 2 (GJB2) gene were amplified and sequenced.</p><p><b>RESULTS</b>Clinical evaluation revealed a wide range of severity, age-at-onset and audiometric configuration of hearing impairment in the matrilineal relatives in these families. The penetrance rates of hearing loss in these pedigrees were 17.6%, 50.0%, 66.7%, 31.3% and 23.1%, with an average of 37.7%, when aminoglycoside-induced deafness was included. Sequence analysis of the complete mitochondrial genomes in these pedigrees identified the known 1555A>G mutation and distinct sets of mitochondrial DNA(mtDNA) polymorphisms belonging to Eastern Asian haplogroups D4b2b, B4c1b1, F3, C1 and D5a, respectively. Of these variants, ND1 L89T and CO3 A200T mutations resided at the highly conservative regions. However, there were no functionally significant mutations in tRNAs and rRNAs or secondary known mutations. No hearing loss related GJB2 gene mutation was observed.</p><p><b>CONCLUSION</b>The lack of significant mutation in the ruled out the possible involvement of GJB2 in the phenotypic expression of the 1555A>G mutation in those affected subjects. However, aminoglycosides, mtDNA variations and other nuclear modifier genes may play an important role in the phenotypic manifestation of the 1555A>G mutation in these Chinese families.</p>
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Índice:
WPRIM
Asunto principal:
Linaje
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Análisis Mutacional de ADN
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Datos de Secuencia Molecular
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Etnicidad
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Química
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China
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Secuencia de Aminoácidos
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Conexinas
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Patrón de Herencia
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Pueblo Asiatico
Límite:
Animals
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Female
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Humans
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Male
País/Región como asunto:
Asia
Idioma:
Zh
Revista:
Chinese Journal of Medical Genetics
Año:
2011
Tipo del documento:
Article