Multi-minicore disease and atypical periodic paralysis associated with novel mutations in the skeletal muscle ryanodine receptor (RYR1) gene

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• 作者：Haiyan Zhou ; Suzanne Lillis ; Ryan E. Loy ; Farshid Ghassemi ; Michael R. Rose ; Fiona Norwood ; Kerry Mills ; Safa Al-Sarraj ; Russell J.M. Lane ; Lucy Feng ; Emma Matthews ; Caroline A. Sewry ; Stephen Abbs ; S
• 关键词：Multi-minicore disease (MmD) ; Periodic paralysis ; Excitation– ; contraction coupling (ECC) ; Skeletal muscle ryanodine receptor (RYR1) gene
• 刊名：Neuromuscular Disorders
• 出版年：2010
• 出版时间：March 2010
• 年：2010
• 卷：20
• 期：3
• 页码：166-173
• 全文大小：923 K

文摘

The skeletal muscle ryanodine receptor plays a crucial role in excitation–contraction (EC) coupling and is implicated in various congenital myopathies. The periodic paralyses are a heterogeneous, dominantly inherited group of conditions mainly associated with mutations in the SCN4A and the CACNA1S genes. The interaction between RyR1 and DHPR proteins underlies depolarization-induced Ca²⁺ release during EC coupling in skeletal muscle. We report a 35-year-old woman presenting with signs and symptoms of a congenital myopathy at birth and repeated episodes of generalized, atypical normokalaemic paralysis in her late teens. Genetic studies of this patient revealed three heterozygous RYR1 substitutions (p.Arg2241X, p.Asp708Asn and p.Arg2939Lys) associated with marked reduction of the RyR1 protein and abnormal DHPR distribution. We conclude that RYR1 mutations may give rise to both myopathies and atypical periodic paralysis, and RYR1 mutations may underlie other unresolved cases of periodic paralysis with unusual features.