TY - JOUR
T1 - Retinitis pigmentosa associated with rhodopsin mutations
T2 - Correlation between phenotypic variability and molecular effects
AU - Iannaccone, Alessandro
AU - Man, David
AU - Waseem, Naushin
AU - Jennings, Barbara J.
AU - Ganapathiraju, Madhavi
AU - Gallaher, Kevin
AU - Reese, Elisheva
AU - Bhattacharya, Shomi S.
AU - Klein-Seetharaman, Judith
N1 - Funding Information:
We acknowledge the generous support of: Research to Prevent Blindness, New York, NY (Career Development Award to AI and unrestricted Grant to UTHSC Ophthalmology); Sofya Kovalevskaya Prize of the Humboldt Foundation, Germany/Zukunftsinvestitionsprogramm der Bundesregierung Deutschland (J.K.S.), National Science Foundation Grants EIA0225636, EIA0225656 and CAREER CC044917 (J.K.S.), and National Institutes of Health Grant NLM108730, USA (J.K.S.); the Special Trustees of Moorfield’s Eye Hospital (S.S.B.). Molecular genetic analyses for the G188R family were originally performed at the following labs: Institute of Medical Genetics, University La Sapienza, Rome, Italy; International Institute of Genetics and Biophysics, Naples, Italy; and Institut für Human Genetik, Universität Lübeck, Germany. The R135L mutation was identified in the laboratory of Dr. Thaddeus P. Dryja, MD, Harvard University, Boston, MA, USA, where also the presence of the P180A change was independently verified.
PY - 2006/12
Y1 - 2006/12
N2 - 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.
AB - 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.
KW - Membrane protein misfolding
KW - Phenotype
KW - Protein stability prediction
KW - Retinitis pigmentosa
KW - Rhodopsin
KW - Visual function
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U2 - 10.1016/j.visres.2006.08.018
DO - 10.1016/j.visres.2006.08.018
M3 - Article
C2 - 17014888
AN - SCOPUS:33750628594
SN - 0042-6989
VL - 46
SP - 4556
EP - 4567
JO - Vision Research
JF - Vision Research
IS - 27
ER -