A novel desmoplakin mutation causes dilated cardiomyopathy with palmoplantar keratoderma as an early clinical sign

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Karvonen , V , Harjama , L , Heliö , K , Kettunen , K , Elomaa , O , Koskenvuo , J W , Kere , J , Weckström , S , Holmström , M , Saarela , J , Ranki , A , Heliö , T & Hannula-Jouppi , K 2022 , ' A novel desmoplakin mutation causes dilated cardiomyopathy with palmoplantar keratoderma as an early clinical sign ' , Journal of the European Academy of Dermatology and Venereology , vol. 36 , no. 8 , pp. 1349-1358 . https://doi.org/10.1111/jdv.18164

Title: A novel desmoplakin mutation causes dilated cardiomyopathy with palmoplantar keratoderma as an early clinical sign
Author: Karvonen, V.; Harjama, L.; Heliö, Krista; Kettunen, K.; Elomaa, O.; Koskenvuo, J. W.; Kere, J.; Weckström, S.; Holmström, M.; Saarela, J.; Ranki, A.; Heliö, T.; Hannula-Jouppi, K.
Contributor organization: Department of Dermatology, Allergology and Venereology
HUS Inflammation Center
Kardiologian yksikkö
HUS Heart and Lung Center
HUSLAB
Institute for Molecular Medicine Finland
HUS Diagnostic Center
Research Programs Unit
STEMM - Stem Cells and Metabolism Research Program
University of Helsinki
HUS Medical Imaging Center
Department of Diagnostics and Therapeutics
Clinicum
Department of Medicine
Date: 2022-08
Language: eng
Number of pages: 10
Belongs to series: Journal of the European Academy of Dermatology and Venereology
ISSN: 0926-9959
DOI: https://doi.org/10.1111/jdv.18164
URI: http://hdl.handle.net/10138/346558
Abstract: Background PPKs represent a heterogeneous group of disorders with hyperkeratosis of palmar and/or plantar skin. PPK, hair shaft abnormalities, cardiomyopathy and arrhythmias can be caused by mutations in desmosomal genes, e.g. desmoplakin (DSP). PPK should trigger genetic testing to reveal mutations with possible related cardiac disease. Objectives To report a large multigenerational family with a novel DSP mutation associated with early-onset PPK and adult-onset cardiomyopathy and arrhythmias. Methods A custom-designed in-house panel of 35 PPK related genes was used to screen mutations in the index patient with focal PPK. The identified DSP mutation was verified by Sanger sequencing. DNA samples from 20 members of the large multigenerational family were sequenced for the DSP mutation. Medical records were reviewed. Clinical dermatological evaluation was performed, including light microscopy of hair samples. Cardiac evaluation included clinical examination, echocardiography, cardiac magnetic resonance imaging (CMR), electrocardiogram (ECG), Holter monitoring and laboratory tests. Results We identified a novel autosomal dominant truncating DSP c.2493delA p.(Glu831Aspfs*33) mutation associated with dilated cardiomyopathy (DCM) with arrhythmia susceptibility and focal PPK as an early cutaneous sign. The mutation was found in nine affected family members, but not in any unaffected members. Onset of dermatological findings preceded cardiac symptoms which were variable and occurred at adult age. Conclusions We report a novel truncating DSP mutation causing focal PPK with varying severity and left ventricular dilatation and ventricular extrasystoles. This finding emphasizes the importance of genetic diagnosis in patients with PPK for clinical counselling and management of cardiomyopathies and arrhythmias.
Subject: palmoplantar keratoderma
dilated cardiomyopathy
genodermatosis
next-generation sequencing
CARDIOVASCULAR MAGNETIC-RESONANCE
VENTRICULAR NON-COMPACTION
WOOLLY HAIR
MULTIPLE ALLERGIES
SEVERE DERMATITIS
PHENOTYPE
GENETICS
DOMAIN
SKIN
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Rights: cc_by_nc
Usage restriction: openAccess
Self-archived version: publishedVersion


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