The Sarcomeric Z-Disc and Z-Discopathies

Table 1

Z-disc proteins involved in human disease.

Name of gene	Type of disease
α actinin (central Z-disc)	Cardiomyopathy
Muscle LIM protein (MLP)	Cardiomyopathy
Telethonin (TCAP)	Cardiomyopathy, LGMD2G
Actin	Cardiomyopathy
Integrin-linked kinase (ILK)	DCM
Calsarcin1 (Myozenin, ZASP)	Cardiomyopathy, myofibrillar myopathy (MFM) zaspopathies
FHL1 (four and a half LIM domain protein)	X-linked myopathy with postural muscle atrophy (XMPMA), scapuloperoneal (SP), reducing body myopathy (RBM)
Cypher (Zasp, Oracle)	Cardiomyopathy, MFM
Desmin (Z-disc related)	Multiple
Nebulin/Nebulette	Nemaline myopathy
Myotilin	LGMD, MFM, myotilinopathy
BAG3	Cardiomyopathy, MFM
Titin (Z-disc)*	Cardiomyopathy (titinopathies)

Z-disc protein mutations cause a wide spectrum of diseases, which may be called “Z-discopathies”. Titin mutation itself cause a broad spectrum of diseases (here we refer only to mutations affecting the Z-disc). The term cardiomyopathy includes at least HCM and DCM, other types of heart failure such as arrhythmogenic right ventricular myopathy.