Ryanodine receptor 1-related disorders: an historical perspective and proposal for a unified nomenclature

Skeletal Muscle

Table 1 Genes associated with main subtypes of RYR1-related myopathies

	Gene	Locus	Inheritance	Prevalence	Protein
Central core disease	RYR1	19q13	AD or AR	>90% [56]	Ryanodine receptor type 1
Central core disease	ACTA1	1q42	AD	Rare	Skeletal α-actin
Core-rod myopathy	RYR1	19q13	AD or AR	Most common cause [2]	Ryanodine receptor type 1
	NEB	2q2	AR	Rare	Nebulin
	KBTBD13	15q25	AD	Rare	Kelch 13
Centronuclear myopathy	RYR1	19q13	AR	Most common cause of AR disease [28]	Ryanodine receptor type 1
	DNM2	19p13	AD	Most common cause of AD disease [2]	Dynamin-2
	BIN1	2q14	AR	Rare	Amphiphysin
	CCDC78	16p13.3	AD	Rare	Coiled-coil domain-containing protein 78
± cardiomyopathy	TTN	2q31	AR	Rare	Titin
Myotubular myopathy	MTM1	Xq28	XLR	Most common cause in severely affected males [57]	Myotubularin
Congenital fiber-type disproportion	TPM3	1q2	AD	25-50% [58]	α-tropomyosin
	RYR1	19q13	AR	~20% [59]	Ryanodine receptor type 1
	ACTA1	1q42	AD	Rare	Skeletal α-actin
	TPM2	9q13	AD	Rare	β-tropomyosin
	SELENON	1p36	AR	Rare	Selenoprotein N
± cardiomyopathy	MYH7	14q11	AD	Rare	Slow myosin heavy chain
	HACD1	10p12	AR	Rare	3-hydroxyacyl-CoA dehydratase 1
+ cardiomyopathy	Unidentified gene	Xp22.13 to Xq22.1	XLR	Rare	?
Multi-minicore disease	SELENON	1p36	AR	~50% [60]^a	Selenoprotein N
Multi-minicore disease	RYR1	19q13	AR	Second most common cause [61]	Ryanodine receptor type 1
± cardiomyopathy	MYH7	14q11	AR	Uncommon	Slow myosin heavy chain
+ cardiomyopathy	ACTA1	1q42	AD	Rare	Skeletal α-actin
+ cardiomyopathy	DES	2q35	?	Rare	Desmin
+ cardiomyopathy	LMNA	1q22	?	Rare	Lamin A/C

Adapted from Jungbluth, Sewry, & Muntoni, The Congenital Myopathies, in Rosenberg’s Molecular and Genetic Basis of Neurological and Psychiatric Diseases, Chapter 93, 5^th edition
Abbreviations: AD autosomal dominant, AR autosomal recessive, XLR X-linked recessive
^aclassic MmD phenotype. Only the most common genetic backgrounds and predominant modes of inheritance are indicated

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