SCIENTIFIC JOURNAL of the Hungarian Society of Cardiology

Identification of a titin and desmoplakin double gene mutation in peripartum cardiomyopathy: genetic analysis of the first patient with heart transplantation performed in Szeged

█ Case report

DOI: 10.26430/CHUNGARICA.2020.50.2.132

Csányi Beáta1, Bogáts Gábor1, Rudas László2, Babik Barna2, Nagy Viktória1, Tringer Annamária1, Hategan Lidia1, Borbás János1, Hegedűs Zoltán3,4,
Nagy István5,6, Sepp Róbert1
1Szegedi Tudományegyetem, II. sz. Belgyógyászati Klinika és Kardiológiai Központ, Szeged
2Szegedi Tudományegyetem, Aneszteziológiai és Intenzív Terápiás Intézet, Szeged
3Biofizikai Intézet, Szegedi Biológiai Központ, Szeged
4Pécsi Tudományegyetem, Biokémiai és Orvosi Kémiai Intézet, Pécs
5Biokémiai Intézet, Szegedi Biológiai Központ, Szeged
6Seqomics Biotechnológiai Kft.


Peripartum cardiomyopathy (PPC) is an idiopathic cardiomyopathy presenting with heart failure secondary to left ven­tricular systolic dysfunction towards the end of pregnancy or in the months following delivery, when no other cause of heart failure is found. Data support the observation that PPC and dilated cardiomyopathy (DCM) share a similar genetic background in a number of cases.
We performed genetic analysis of a 36-years-old female patient who underwent heart transplantation due to PPC in Szeged. The patient, with her second pregnancy, was admitted to our Institution at 38 weeks of gestation because of dyspnea. Echocardiography showed a dilated left ventricle with reduced left ventricular ejection fraction (EF: 30%). Symp­toms of heart failure progressed despite of intensive treatment including levosimendan, dopamine, dobutamine and IABP support. The left ventricular function further deteriorated (EF: 14%), low cardiac output syndrome (CI: 1.4 l/min/m2, SV: 21 ml) developed, and mechanical ventilation was necessary because of hypoxia. Due to the life-threaten­ing clinical situation, the only solution was urgent heart transplantation, which was carried out in Szeged, as the patient was unsuitable for transport. Family screening revealed that her mother had dilated cardiomyopathy. Based on this, familial cardiomyopathy was suspected, and genetic screening was performed.
Genotyping was performed by next generation sequencing, with a platform including 103 causative cardiomyopathy genes. Genetic screening detected 5 variants, and two of them were pathogenic with a truncation effect, one in the titin gene (TTN p.Arg13527Stop) and another in the desmoplakin gene (DSP p.Arg2284Stop). The pathogenic variants predispose to lose normal protein function either by protein truncation or nonsense-mediated mRNA decay. The p.Arg13527Stop variant in the TTN gene has been reported in association with DCM and the p.Arg2284Stop variant in the DSP gene has been published previously in association with ARVD/C and Carvajal-syndrome. So far, no case of these two pathogenic variants occurring together has been published.
Our case highlights the fact that some of the PPCs may have genetic origin. A family screening should be per­formed in each patient and genetic screening when suspicion arises.


click here to read the full article

click here to read the pdf