Optic atrophy and sensorineural hearing loss in a family caused by an R445H OPA1 mutation.
Autosomal dominant optic atrophy (ADOA) is the most common form of inherited optic atrophy. Four genetic loci have been associated with ADOA: OPA1, OPA2, OPA3, and OPA4. Out of these four loci, only one gene has been identified, OPA1. We previously described a unique syndrome of optic atrophy, sensorineural hearing loss, ptosis, and ophthalmoplegia in two unrelated families associated with an R445H mutation in OPA1. The R445H mutation is the only OPA1 mutation that has been associated with this syndrome. In this manuscript, we clinically characterize an unrelated family with four members affected by optic atrophy and hearing loss without extraocular motility abnormalities or ptosis. This family also harbors the R445H mutation. These cases help illustrate the intra- and inter-family variability in phenotype associated with this mutation. As we continue to learn more about OPA1 and the function of its protein product, we will begin to understand the pathophysiology of optic atrophy. This understanding will ultimately lead to novel treatments directed toward preventing the visual loss and disability associated with this inherited disease.
Li
Chunmei
C
Department of Ophthalmology and Visual Sciences, University of Utah Health Sciences Center, Salt Lake City, UT 84132, USA.
Kosmorsky
Gregory
G
Zhang
Kang
K
Katz
Bradley J
BJ
Ge
Jian
J
Traboulsi
Elias I
EI
D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics*; D001120:Arginine / Q000235:genetics; D002648:Child; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics* / Q000502:physiology; D008040:Genetic Linkage; D006239:Haplotypes; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006320:Hearing Tests; D006639:Histidine / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D029241:Optic Atrophy, Autosomal Dominant / Q000235:genetics*
D006639:Histidine; D001120:Arginine; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human