title: Homozygous Desmocollin-2 Mutations and Arrhythmogenic Cardiomyopathy.
abstract: Dominant mutations in desmocollin-2 (DSC2) gene cause arrhythmogenic cardiomyopathy (ACM), a progressive heart muscle disease characterized by ventricular tachyarrhythmias, heart failure, and risk of juvenile sudden death. Recessive mutations are rare and are associated with a cardiac or cardiocutaneous phenotype. Here, we evaluated the impact of a homozygous founder DSC2 mutation on clinical expression of ACM. An exon-by-exon analysis of the DSC2 coding region was performed in 94 ACM index patients. The c.536A>G (p.D179G) mutation was identified in 5 patients (5.3%), 4 of which resulted to be homozygous carriers. The 5 subjects shared a conserved haplotype, strongly indicating a common founder. Genetic and clinical investigation of probands' families revealed that p.D179G homozygous carriers displayed severe forms of biventricular cardiomyopathy without hair or skin abnormalities. The only heterozygous proband, who carried an additional variant of unknown significance in αT-catenin gene, showed a mild form of ACM without left ventricular involvement. All heterozygous family members were clinically asymptomatic. In conclusion, this is the first homozygous founder mutation in DSC2 gene identified among Italian ACM probands. Our findings provide further evidence of the occurrence of recessive DSC2 mutations in patients with ACM predominantly presenting with biventricular forms of the disease.
authors: Department of Biology, University of Padua, Padua, Italy.
authors: Alessandra
authors: A
authors: Lorenzon
authors: Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua, Padua, Italy.
authors: Kalliopi
authors: K
authors: Pilichou
authors: Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua, Padua, Italy.
authors: Ilaria
authors: I
authors: Rigato
authors: Department of Biology, University of Padua, Padua, Italy.
authors: Giovanni
authors: G
authors: Vazza
authors: Department of Biology, University of Padua, Padua, Italy.
authors: Marzia
authors: M
authors: De Bortoli
authors: Department of Biology, University of Padua, Padua, Italy.
authors: Martina
authors: M
authors: Calore
authors: Department of Biology, University of Padua, Padua, Italy.
authors: Gianluca
authors: G
authors: Occhi
authors: Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua, Padua, Italy.
authors: Elisa
authors: E
authors: Carturan
authors: Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua, Padua, Italy.
authors: Elisabetta
authors: E
authors: Lazzarini
authors: Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua, Padua, Italy.
authors: Marco
authors: M
authors: Cason
authors: Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua, Padua, Italy.
authors: Elisa
authors: E
authors: Mazzotti
authors: Department of Biology, University of Padua, Padua, Italy.
authors: Giulia
authors: G
authors: Poloni
authors: Department of Biology, University of Padua, Padua, Italy.
authors: Maria Luisa
authors: ML
authors: Mostacciuolo
authors: Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua, Padua, Italy.
authors: Luciano
authors: L
authors: Daliento
authors: Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua, Padua, Italy.
authors: Gaetano
authors: G
authors: Thiene
authors: Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua, Padua, Italy.
authors: Domenico
authors: D
authors: Corrado
authors: Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua, Padua, Italy.
authors: Cristina
authors: C
authors: Basso
authors: Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua, Padua, Italy.
authors: Barbara
authors: B
authors: Bauce
authors: Department of Biology, University of Padua, Padua, Italy. Electronic address: alessandra.rampazzo@unipd.it.
authors: Alessandra
authors: A
authors: Rampazzo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics*; D002648:Child; D051187:Desmocollins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D018703:Founder Effect; D006720:Homozygote; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D055815:Young Adult
chemical_list: C081561:DSC2 protein, human; D051187:Desmocollins