OPA1 R445H mutation in optic atrophy associated with sensorineural deafness.
The heterozygous R445H mutation in OPA1 was found in five patients with optic atrophy and deafness. Audiometry suggested that the sensorineural deafness resulted from auditory neuropathy. Skin fibroblasts showed hyperfragmentation of the mitochondrial network, decreased mitochondrial membrane potential, and adenosine triphosphate synthesis defect. In addition, OPA1 was found to be widely expressed in the sensory and neural cochlear cells of the guinea pig. Thus, optic atrophy and deafness may be related to energy defects due to a fragmented mitochondrial network.
Amati-Bonneau
Patrizia
P
INSERM U694, Laboratoire de Biochimie et Biologie Moléculaire, Centre Hospitalier Universitaire, F-49033 Angers, France.
Guichet
Agnès
A
Olichon
Aurélien
A
Chevrollier
Arnaud
A
Viala
Frédérique
F
Miot
Stéphanie
S
Ayuso
Carmen
C
Odent
Sylvie
S
Arrouet
Catherine
C
Verny
Christophe
C
Calmels
Marie-Noelle
MN
Simard
Gilles
G
Belenguer
Pascale
P
Wang
Jing
J
Puel
Jean-Luc
JL
Hamel
Christian
C
Malthièry
Yves
Y
Bonneau
Dominique
D
Lenaers
Guy
G
Reynier
Pascal
P
D000293:Adolescent; D000328:Adult; D000818:Animals; D001299:Audiometry; D002648:Child; D003051:Cochlea / Q000378:metabolism; D006224:Cricetinae; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics*; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D029241:Optic Atrophy, Autosomal Dominant / Q000235:genetics* / Q000378:metabolism; D010101:Oxygen Consumption; D010641:Phenotype; D017354:Point Mutation; D012867:Skin / Q000166:cytology
D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human