Case reports of two pedigrees with recessive arrhythmogenic right ventricular cardiomyopathy associated with homozygous Thr335Ala variant in DSG2

Autor: Miia Holmström, Tiina Heliö, Eija H. Seppälä, Sami Qadri, Olli Anttonen, Juha Koskenvuo, Samuel Myllykangas, Tero-Pekka Alastalo, Juho Viikilä
Přispěvatelé: Department of Medicine, Clinicum, HUS Heart and Lung Center, Kardiologian yksikkö, Medicum, University of Helsinki, Biosciences, Children's Hospital, HUS Children and Adolescents, HUS Medical Imaging Center, Department of Diagnostics and Therapeutics
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
Proband
palmoplantaarinen keratoderma
DYSPLASIA/CARDIOMYOPATHY
Case Report
030204 cardiovascular system & hematology
PALMOPLANTAR KERATODERMA
DSG2
SUDDEN DEATH
0302 clinical medicine
Missense mutation
arytmogeeninen oikean kammion dysplasia
äkkikuolema
desmosomit
Arrhythmogenic Right Ventricular Dysplasia
Genetics (clinical)
variantti
Aged
80 and over
Genetics
Desmoglein 2
arytmogeeninen oikean kammion kardiomyopatia
tapausselostus
Homozygote
vallitsevuus
High-Throughput Nucleotide Sequencing
Heart
Dilated cardiomyopathy
Desmosomes
Middle Aged
Magnetic Resonance Imaging
Penetrance
PREVALENCE
Pedigree
3. Good health
Female
Cardiomyopathies
desmosomaaliset mutaatiot
Heterozygote
lcsh:Internal medicine
esiintyvyys
lcsh:QH426-470
Genetic counseling
Mutation
Missense
Desmoglein-2
Biology
Polymorphism
Single Nucleotide
Sudden death
Right ventricular cardiomyopathy
DESMOSOMAL MUTATIOS
tapaustutkimus
Young Adult
03 medical and health sciences
dysplasia
medicine
Humans
Case series
lcsh:RC31-1245
Aged
kardiomyopatiat
Sequence Analysis
DNA
DILATED CARDIOMYOPATHY
medicine.disease
lcsh:Genetics
030104 developmental biology
variant
3121 General medicine
internal medicine and other clinical medicine
mutaatio
Mutation
WOOLLY HAIR
3111 Biomedicine
dilatoiva kardiomyopatia
Arrhythmogenic right ventricular cardiomyopathy
Zdroj: BMC Medical Genetics, Vol 18, Iss 1, Pp 1-9 (2017)
BMC Medical Genetics
ISSN: 1471-2350
DOI: 10.1186/s12881-017-0442-3
Popis: 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. Electronic supplementary material The online version of this article (doi:10.1186/s12881-017-0442-3) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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