Maternally inherited hearing loss in a large kindred with a novel T7511C mutation in the mitochondrial DNA tRNA(Ser(UCN)) gene.
Thirty-six of 43 maternally related members of a large African American family experienced hearing loss. A muscle biopsy specimen from the proband showed cytochrome c oxidase (COX)-deficient fibers but no ragged-red fibers; biochemical analysis showed marked reduction of COX activity. A novel T7511C point mutation in the tRNA(Ser(UCN)) gene was present in almost homoplasmic levels (>95%) in the blood of 18 of 20 family members, and was also found in lower abundance in the other two. Single-fiber PCR showed that the mutational load was greater in COX-deficient muscle fibers. The tRNA(ser(UCN)) gene may be a "hot spot" for mutations associated with maternally transmitted hearing loss.
Sue
C M
CM
Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Tanji
K
K
Hadjigeorgiou
G
G
Andreu
A L
AL
Nishino
I
I
Krishna
S
S
Bruno
C
C
Hirano
M
M
Shanske
S
S
Bonilla
E
E
Fischel-Ghodsian
N
N
DiMauro
S
S
Friedman
R
R
D000328:Adult; D004272:DNA, Mitochondrial / Q000235:genetics*; D003638:Deafness / Q000235:genetics*; D005260:Female; D006801:Humans; D009035:Mothers; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012362:RNA, Transfer, Ser / Q000235:genetics*
D004272:DNA, Mitochondrial; D012362:RNA, Transfer, Ser