Two large Spanish pedigrees with nonsyndromic sensorineural deafness and the mtDNA mutation at nt 1555 in the 12s rRNA gene: evidence of heteroplasmy.
We describe two unrelated Spanish families with isolated sensorineural hearing loss. In both pedigrees, the deafness was transmitted maternally, which suggested a mitochondrial, DNA (mtDNA) defect. Within the same pedigree, some relatives showed aminoglycoside-induced deafness, whereas others were not exposed to aminoglycosides before the onset of hearing loss. Molecular genetic analysis in both families showed the A-to-G transition at nt 1555 (A1555G) in the mitochondrial 12S rRNA gene. In one pedigree, the mutation was homoplasmic; in the other, it was heteroplasmic. To assess the frequency of this mutation, we screened 42 patients of various ethnic backgrounds with isolated sensorineural hearing loss; none harbored the A1555G mutation. This is the first report of heteroplasmy in a family with isolated sensorineural deafness associated with the A1555G mutation.
el-Schahawi
M
M
H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, Department of Neurology, Columbia-Presbyterian Medical Center, New York, NY 10032, USA.
López de Munain
A
A
Sarrazin
A M
AM
Shanske
A L
AL
Basirico
M
M
Shanske
S
S
DiMauro
S
S
D000595:Amino Acid Sequence; D004272:DNA, Mitochondrial / Q000235:genetics*; D003638:Deafness / Q000235:genetics*; D005260:Female; D006630:Hispanic or Latino; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D010375:Pedigree; D011247:Pregnancy; D012335:RNA, Ribosomal / Q000235:genetics*
D004272:DNA, Mitochondrial; D015345:Oligonucleotide Probes; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S