Homozygous Desmocollin-2 Mutations and Arrhythmogenic Cardiomyopathy.
Am J Cardiol
; 116(8): 1245-51, 2015 Oct 15.
Article
en En
| MEDLINE
| ID: mdl-26310507
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Displasia Ventricular Derecha Arritmogénica
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Desmocolinas
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Mutación
Tipo de estudio:
Prognostic_studies
Límite:
Adolescent
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Adult
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Aged
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Aged80
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Child
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Female
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Humans
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Male
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Middle aged
País/Región como asunto:
Europa
Idioma:
En
Revista:
Am J Cardiol
Año:
2015
Tipo del documento:
Article
País de afiliación:
Italia