Retinitis pigmentosa associated with rhodopsin mutations: Correlation between phenotypic variability and molecular effects.
Similar retinitis pigmentosa (RP) phenotypes can result from mutations affecting different rhodopsin regions, and distinct amino acid substitutions can cause different RP severity and progression rates. Specifically, both the R135L and R135W mutations (cytoplasmic end of H3) result in diffuse, severe disease (class A), but R135W causes more severe and more rapidly progressive RP than R135L. The P180A and G188R mutations (second intradiscal loop) exhibit a mild phenotype with regional variability (class B1) and diffuse disease of moderate severity (class B2), respectively. Computational and in vitro studies of these mutants provide molecular insights into this phenotypic variability.
Iannaccone
Alessandro
A
Hamilton Eye Institute, Department of Ophthalmology, Retinal Degeneration and Ophthalmic Genetics Service, University of Tennessee Health Science Center, 930 Madison Avenue, Suit 731, Memphis, TN 38163, USA.
Man
David
D
Waseem
Naushin
N
Jennings
Barbara J
BJ
Ganapathiraju
Madhavi
M
Gallaher
Kevin
K
Reese
Elisheva
E
Bhattacharya
Shomi S
SS
Klein-Seetharaman
Judith
J
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D019295:Computational Biology; D004252:DNA Mutational Analysis; D018450:Disease Progression; D004596:Electroretinography; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010446:Peptide Fragments / Q000235:genetics; D010641:Phenotype; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000378:metabolism; D012243:Rhodopsin / Q000235:genetics* / Q000378:metabolism; D012374:Rod Cell Outer Segment / Q000378:metabolism; D014785:Vision, Ocular
D010446:Peptide Fragments; D012243:Rhodopsin