Table 2.

Secondary triadopathies

Disorder	Gene(s)	Relationship to Triad
Myotonic dystrophy type I	DMPK (CTG repeat expansion in 3’UTR)	Abnormal splicing of key triad gene products (RyR1, DHPR, and BIN1), leading to abnormal EC coupling and altered muscle histopathology
Dystrophinopathies	DMD	Hypernitrosylated RyR1 leading to chronic channel “leakiness”
Sarcoglycanopathies	SGCA, SGCB, SGCD, and SGCG	Hypernitrosylated RyR1 leading to chronic channel “leakiness”
Dysferlinopathies	DYSF	Dysferlin is a T-tubule component. May stabilize T-tubule and/or chaperone triad proteins
Calpainopathies	CAPN3	Partial localization to the triad. Loss of CAPN3 associated with reduced RyR1 expression
SEPN1-related myopathies	SEPN1	Histopathology similar to RYR1-related myopathies. Direct interaction with RyR1
CCDC78-associated myopathy	CCDC78	Partial localization to the triad. Mutation associated with RyR1 accumulation and abnormal triad structure

UTR = untranslated region; RyR1 = ryanodine receptor; DHPR = dihydropyridine receptor; BIN1 = bridging integrator 1; EC = excitation–contraction; CAPN3 = calpain-3