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Desmin accumulation restrictive cardiomyopathy and atrioventricular block associated with desmin gene defects
Author(s) -
Arbustini Eloisa,
Pasotti Michele,
Pilotto Andrea,
Pellegrini Carlo,
Grasso Maurizia,
Previtali Stefano,
Repetto Alessandra,
Bellini Ornella,
Azan Gaetano,
Scaffino Manuela,
Campana Carlo,
Piccolo Giovanni,
Viganò Mario,
Tavazzi Luigi
Publication year - 2006
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1016/j.ejheart.2005.11.003
Subject(s) - desmin , exon , restrictive cardiomyopathy , cardiomyopathy , proband , medicine , mutation , phenotype , genetics , gene , pathology , biology , microbiology and biotechnology , heart failure , immunohistochemistry , vimentin
Background Primary desminopathies are caused by desmin gene [ DES (MIM*125660)] mutations. The clinical spectrum includes pure myopathies, cardiomuscular diseases and cardiomyopathies. Patients with restrictive cardiomyopathy (RCM) plus atrioventricular block (AVB) due to DES defects are frequently unrecognized unless desmin accumulation is specifically investigated in endomyocardial biopsy (EMB) by ultrastructural study. Aims To describe a cardiological phenotype characterized by RCM plus AVB due to desmin accumulation caused by DES defects. Methods and results Desmin accumulation was diagnosed by means of ultrastructural and immunocytochemical studies of EMB in four unrelated probands with RCM and AVB. Candidate genes [ DES and αB‐crystallin ( CRYAB )] were screened using sequence analysis. Four DES gene mutations were identified: three new (R16C, T453I and a 10 bp deletion at the exon—intron boundary of exon 3 disrupting the donor splice site) and one known (R406W). The disease was autosomal dominant in two families, recessive in one and associated with a de novo mutation in one. The mutations cosegregated with phenotype in all patients. CRYAB gene screening was negative. Conclusions A cardiac phenotype characterized by RCM and AVB caused by desmin accumulation is associated with DES mutations. Although the mutations affected different domains, the cardiac phenotype was identical.