Prevalence and clinical features of the mitochondrial m.1555A>G mutation in Taiwanese patients with idiopathic sensorineural hearing loss and association of haplogroup F with low penetrance in three families
Journal
Ear and Hearing
Journal Volume
28
Journal Issue
3
Pages
332-342
Date Issued
2007
Author(s)
Abstract
OBJECTIVE: The m.1555A>G mutation in the mitochondria 12S rRNA gene has been reported to be an important cause of nonsyndromic hereditary hearing loss. However, remarkable interfamilial and intrafamilial variations in the phenotypes of the mutation preclude precise prognosis during genetic counseling. Hence, this study was performed to explore the factors that might contribute to the differences in the phenotypes, including aminoglycoside exposure, mutation load and mitochondrial DNA (mtDNA) background. Also reported were the prevalence and the clinical features of the m.1555A>G mutation in the hearing-impaired Taiwanese patients. DESIGN: Mutations in the 12S rRNA gene were screened in a panel of 315 unrelated Taiwanese families with idiopathic sensorineural hearing loss. The clinical features in families with m.1555A>G mutation were analyzed, and the roles of aminoglycoside exposure, mutation load and mtDNA background in disease expression were investigated. Penetrance was then compared among families with different mtDNA backgrounds. RESULTS: The m.1555A>G mutation was identified in a total of 10 (3.2%) families, and was characterized clinically by progressive, postlingual and bilaterally symmetric sensorineural hearing loss and normal temporal bone radiological results. The m.1555A>G mutation was homoplasmic (i.e., all the mitochondrial DNA carries the mutation) in all the matrilineal relatives in these 10 pedigrees. Among the 44 hearing-impaired relatives of the 10 pedigrees, only two recalled definite episodes of aminoglycoside-induced hearing loss. mtDNA backgrounds in these 10 families could be categorized into 6 main haplogroups (A, B, D, F, M7, N*), including three families belonging to haplogroup F, two belonging to haplogroup A, two belonging to haplogroup M7, and three belonging to haplogroups B, N* and D, respectively. Penetrance differed among various haplogroups, and certain haplogroups appeared to be associated with a lower penetrance, like the three haplogroup F families, in which the penetrance ranged from 13 to 33%. Further analysis confirmed a heterogeneous distribution of hearing-impaired subjects among various haplogroups (Chi-square test, p = 0.018). CONCLUSIONS: The mitochondrial m.1555A>G mutation accounted for 3.2% of the Taiwanese families (0% of the simplex families and 11% of multiplex families respectively) with sensorineural hearing impairment of unknown etiology. Since it was identified in a variety of mtDNA backgrounds, the mutation appeared to arise from multiple origins in Taiwanese. As subjects with various haplogroups demonstrated different penetrance, mtDNA background might exert effects on the disease expression of the m.1555A>G mutation. ? 2007 Lippincott Williams & Wilkins, Inc.
SDGs
Other Subjects
adenine; guanine; mitochondrial DNA; ribosome RNA; adult; amino acid substitution; article; clinical article; clinical feature; female; gene mutation; genetic association; genetic screening; genetic variability; haplotype; heterozygosity; human; male; mitochondrial gene; nucleotide sequence; ototoxicity; pedigree; penetrance; perception deafness; phenotype; RNA gene; school child; screening test; Taiwan; temporal bone
Publisher
Lippincott Williams and Wilkins
Type
journal article