Case reports of two pedigrees with recessive arrhythmogenic right ventricular cardiomyopathy associated with homozygous Thr335Ala variant in DSG2
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Qadri , S , Anttonen , O , Viikila , J , Seppälä , E H , Myllykangas , S , Alastalo , T-P , Holmström , M , Helio , T & Koskenvuo , J W 2017 , ' Case reports of two pedigrees with recessive arrhythmogenic right ventricular cardiomyopathy associated with homozygous Thr335Ala variant in DSG2 ' , BMC Medical Genetics , vol. 18 , 86 . https://doi.org/10.1186/s12881-017-0442-3
| Title: | Case reports of two pedigrees with recessive arrhythmogenic right ventricular cardiomyopathy associated with homozygous Thr335Ala variant in DSG2 |
| Author: | Qadri, Sami; Anttonen, Olli; Viikila, Juho; Seppälä, Eija H.; Myllykangas, Samuel; Alastalo, Tero-Pekka; Holmström, Miia; Helio, Tiina; Koskenvuo, Juha W. |
| Contributor organization: | Doctoral Programme in Clinical Research Medicum University of Helsinki Biosciences Clinicum Children's Hospital HUS Children and Adolescents HUS Medical Imaging Center Department of Diagnostics and Therapeutics Department of Medicine Kardiologian yksikkö HUS Heart and Lung Center |
| Date: | 2017-08-17 |
| Language: | eng |
| Number of pages: | 9 |
| Belongs to series: | BMC Medical Genetics |
| ISSN: | 1471-2350 |
| DOI: | https://doi.org/10.1186/s12881-017-0442-3 |
| URI: | http://hdl.handle.net/10138/224209 |
| Abstract: | Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiac disease, involving changes in ventricular myocardial tissue and leading to fatal arrhythmias. Mutations in desmosomal genes are thought to be the main cause of ARVC. However, the exact molecular genetic etiology of the disease still remains largely inconclusive, and this along with large variabilities in clinical manifestations complicate clinical diagnostics. Case presentation: We report two families (n = 20) in which a desmoglein-2 (DSG2) missense variant c. 1003A > G, p.(Thr335Ala) was discovered in the index patients using next-generation sequencing panels. The presence of this variant in probands' siblings and children was studied by Sanger sequencing. Five homozygotes and nine heterozygotes were found with the mutation. Participants were evaluated clinically where possible, and available medical records were obtained. All patients homozygous for the variant fulfilled the current diagnostic criteria for ARVC, whereas none of the heterozygous subjects had symptoms suggestive of ARVC or other cardiomyopathies. Conclusions: The homozygous DSG2 variant c. 1003A > G co-segregated with ARVC, indicating autosomal recessive inheritance and complete penetrance. More research is needed to establish a detailed understanding of the relevance of rare variants in ARVC associated genes, which is essential for informative genetic counseling and rational family member testing. |
| Subject: |
Arrhythmogenic right ventricular cardiomyopathy
Cardiomyopathies Desmosomes DSG2 Mutation Case series DESMOSOMAL MUTATION CARRIERS PROTEIN GENE-MUTATIONS TASK-FORCE CRITERIA DILATED CARDIOMYOPATHY PALMOPLANTAR KERATODERMA SUDDEN-DEATH WOOLLY HAIR DYSPLASIA/CARDIOMYOPATHY DYSPLASIA PREVALENCE 3111 Biomedicine 3121 General medicine, internal medicine and other clinical medicine |
| Peer reviewed: | Yes |
| Rights: | cc_by |
| Usage restriction: | openAccess |
| Self-archived version: | publishedVersion |
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