The first publication that associated LMNA variants with ARVC was published in 2012 and reported four patients without desmosomal variants that carried LMNA variants (22199124). These patients met 2010 TCC for ARVC and two had microscopic tissue evaluation confirming interstitial fibrosis and fatty replacement suggesting ARVC phenotype. One variant, p. Arg644Cys under 2015 ACMG criteria no longer is classified as a pathogenic variant. This study also included experimental evidence as immunohistochemistry staining of the biopsies did show delocalization of plakoglobin, which has been reported as pathologic for ARVC phenotype. Another study (25837155) in 2015 showed segregation in a large Italian family; however only the proband met ARVC TFC, the remaining 7 affected individuals only met borderline criteria for ARVC. Another study in 2016 (26620845) identified two LMNA variants in two probands. One only met borderline ARVC criteria with severe RV involvement and frequent PVCs. Experimental evidence was included as RV endomyocardial biopsy did demonstrate fibrous tissue replacement of the myocardium. LMNA mutations associated with ARVC appear to be very rare and the observed phenotypes frequently overlap with dilated cardiomyopathy with conduction system abnormalities and atrial arrhythmias.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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