Loss of function pathogenic variants (nonsense, splicing, deletion/duplication) comprise the overwhelming majority of LAMP2, Danon disease causing mutations to date. Experimental data supports a model where LAMP2 protein deficiency is the major cause of Danon disease. The fact that LAMP2 protein deficiency is complete in males and partial in females is believed to explain some of the differences in disease onset and severity between males and females. LAMP2 protein functions in the autophagy (predominantly macroautophagy) cellular processes and perturbation of normal autophagic function is central to the current model of Danon disease pathogenesis.
LAMP2