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- W2889332297 abstract "Variants in the skeletal muscle ryanodine receptor 1 gene (RYR1) result in a spectrum of RYR1-related disorders. Presentation during infancy is typical and ranges from delayed motor milestones and proximal muscle weakness to severe respiratory impairment and ophthalmoplegia. We aimed to elucidate correlations between genotype, protein structure and clinical phenotype in this rare disease population. Genetic and clinical data from 47 affected individuals were analyzed and variants mapped to the cryo-EM RyR1 structure. Comparisons of clinical severity, motor and respiratory function and symptomatology were made according to the mode of inheritance and affected RyR1 structural domain(s). Overall, 49 RYR1 variants were identified in 47 cases (dominant/de novo, n = 35; recessive, n = 12). Three variants were previously unreported. In recessive cases, facial weakness, neonatal hypotonia, ophthalmoplegia/paresis, ptosis, and scapular winging were more frequently observed than in dominant/de novo cases (all, p < 0.05). Both dominant/de novo and recessive cases exhibited core myopathy histopathology. Clinically severe cases were typically recessive or had variants localized to the RyR1 cytosolic shell domain. Motor deficits were most apparent in the MFM-32 standing and transfers dimension, [median (IQR) 85.4 (18.8)% of maximum score] and recessive cases exhibited significantly greater overall motor function impairment compared to dominant/de novo cases [79.7 (18.8)% vs. 87.5 (17.7)% of maximum score, p = 0.03]. Variant mapping revealed patterns of clinical severity across RyR1 domains, including a structural plane of interest within the RyR1 cytosolic shell, in which 84% of variants affected the bridging solenoid. We have corroborated genotype-phenotype correlations and identified RyR1 regions that may be especially sensitive to structural modification." @default.
- W2889332297 created "2018-09-07" @default.
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- W2889332297 date "2018-08-28" @default.
- W2889332297 modified "2023-10-13" @default.
- W2889332297 title "Correlation of phenotype with genotype and protein structure in RYR1-related disorders" @default.
- W2889332297 cites W114727866 @default.
- W2889332297 cites W1490669493 @default.
- W2889332297 cites W1558371851 @default.
- W2889332297 cites W1572941862 @default.
- W2889332297 cites W1884824544 @default.
- W2889332297 cites W1965603501 @default.
- W2889332297 cites W1972624141 @default.
- W2889332297 cites W1976843038 @default.
- W2889332297 cites W1977565611 @default.
- W2889332297 cites W1982180466 @default.
- W2889332297 cites W1984576497 @default.
- W2889332297 cites W1989826892 @default.
- W2889332297 cites W1990198407 @default.
- W2889332297 cites W1991478255 @default.
- W2889332297 cites W1996899100 @default.
- W2889332297 cites W2000931006 @default.
- W2889332297 cites W2001331591 @default.
- W2889332297 cites W2003907635 @default.
- W2889332297 cites W2006535030 @default.
- W2889332297 cites W2015120617 @default.
- W2889332297 cites W2016121717 @default.
- W2889332297 cites W2020177040 @default.
- W2889332297 cites W2020685420 @default.
- W2889332297 cites W2023379938 @default.
- W2889332297 cites W2027378811 @default.
- W2889332297 cites W2033553632 @default.
- W2889332297 cites W2034220566 @default.
- W2889332297 cites W2034229848 @default.
- W2889332297 cites W2035808268 @default.
- W2889332297 cites W2036331049 @default.
- W2889332297 cites W2039433998 @default.
- W2889332297 cites W2044573154 @default.
- W2889332297 cites W2047664621 @default.
- W2889332297 cites W2047912758 @default.
- W2889332297 cites W2050057821 @default.
- W2889332297 cites W2052436987 @default.
- W2889332297 cites W2057359669 @default.
- W2889332297 cites W2058998963 @default.
- W2889332297 cites W2062804279 @default.
- W2889332297 cites W2063642946 @default.
- W2889332297 cites W2065896050 @default.
- W2889332297 cites W2075971623 @default.
- W2889332297 cites W2077176055 @default.
- W2889332297 cites W2084821192 @default.
- W2889332297 cites W2086836718 @default.
- W2889332297 cites W2103290447 @default.
- W2889332297 cites W2111424481 @default.
- W2889332297 cites W2111644869 @default.
- W2889332297 cites W2112906555 @default.
- W2889332297 cites W2115725862 @default.
- W2889332297 cites W2121573810 @default.
- W2889332297 cites W2121865351 @default.
- W2889332297 cites W2125613629 @default.
- W2889332297 cites W2130479394 @default.
- W2889332297 cites W2131909933 @default.
- W2889332297 cites W2135112559 @default.
- W2889332297 cites W2139909390 @default.
- W2889332297 cites W2147075348 @default.
- W2889332297 cites W2152064075 @default.
- W2889332297 cites W2153379369 @default.
- W2889332297 cites W2156405367 @default.
- W2889332297 cites W2164867418 @default.
- W2889332297 cites W2167038632 @default.
- W2889332297 cites W2170817686 @default.
- W2889332297 cites W2176775630 @default.
- W2889332297 cites W2177197540 @default.
- W2889332297 cites W2179736892 @default.
- W2889332297 cites W2192957804 @default.
- W2889332297 cites W2259446747 @default.
- W2889332297 cites W2269323417 @default.
- W2889332297 cites W2270508964 @default.
- W2889332297 cites W2325217538 @default.
- W2889332297 cites W2332099442 @default.
- W2889332297 cites W2335369961 @default.
- W2889332297 cites W2407911635 @default.
- W2889332297 cites W2419423106 @default.