Fifty-seven papers were reviewed related to RYR2 and ARVD (9628868, 11078270, 11159936, 11807805, 12015469, 12106942, 12169647, 12459180, 12596074, 12919952, 15046075, 15176428, 15336972, 15451514, 15544015, 15831148, 15951021, 16084945, 16096717, 16239587, 16407108, 16733711, 16769042, 16873551, 16873551, 17363426, 17980246, 18326664, 18483626, 18515204, 19029124, 19167631, 19863545, 20045464, 20301310, 21977247, 22068070, 22090716, 22374134, 22450909, 22453944, 23978697, 24447446, 24978818, 25041964, 25411383, 25445213, 26082335, 26743400, 27000522, 27005929, 27548259, 27635072, 28750076, 29497013, 29543670, Rampazzo A et al., Hum Mol Genet 1995). Three publications from the same research group found linkage to chromosome 1q42-q43 and variants in RYR2 in families with right ventricular cardiomyopathy (ARVC2) also described as CPVT with fibro-fatty replacement of the right ventricle (Rampazzo A et al., Hum Mol Genet 1995; 4(11):2151–2154; 11078270; 11159936). A mouse model made from one of the variants (RyR2 R176Q/_ ) found in family 105 that has two variants on one allele (R176Q/T2504M), showed a CPVT like phenotype without evidence of fibrofatty infiltration or structural abnormalities characteristic of arrhythmogenic right ventricular dysplasia (16873551). In several papers RYR2 missense variants were described in possible ARVD index patients. Some of these variants were also relatively often present in reference alleles from the gnomAD database, clear ARVD diagnosis is not provided, segregation information is not informative and/or CPVT was also present in the family (28750076, 26743400, 25041964, 16084945, 27005929). In a recent review it was also recognized that the observed phenotype in the original three publications that reported RYR2 variants in ARVD for the first time should be catecholamine-induced ventricular tachycardia rather than ARVD, and this gene is no longer considered as ARVD causing (29543670). This gene is therefore refuted as a candidate for ARVD.
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