A study in Polish patients with cardiomyopathy emphasizes pathogenicity of phospholamban (PLN) mutations at amino acid position 9 and low penetrance of heterozygous null PLN mutations

BMC Medical Genetics

Rafał Płoski²  Tomasz Zieliński³  Wojciech Drygas⁸  Jerzy Piwoński⁸  Jacek Grzybowski⁹  Łukasz Szumowski¹  Joanna Ponińska⁵  Tomasz Stokłosa⁶  Marcin M Machnicki⁶  Bogna Foss-Nieradko⁴  Przemysław Chmielewski⁴  Łukasz A Małek⁷  Ewa Michalak⁴  Piotr Stawiński⁶  Maria Bilińska¹  Maria Franaszczyk⁵  Małgorzata Sobieszczańska-Małek³  Małgorzata Rydzanicz²  Justyna Śleszycka⁹  Joanna Kosińska²  Zofia T Bilińska⁴  Grażyna T Truszkowska⁵ 

[1] Department of Arrhythmia, Institute of Cardiology, ul. Alpejska 42, Warszawa, 04-628, Poland;Department of Medical Genetics, Warsaw Medical University, ul. Pawińskiego 3C, Warszawa, 02-106, Poland;Department of Heart Failure and Transplantology, Institute of Cardiology, ul. Alpejska 42, Warszawa, 04-628, Poland;Unit for Screening Studies in Inherited Cardiovascular Diseases, Institute of Cardiology, ul. Alpejska 42, Warszawa, 04-628, Poland;Laboratory of Molecular Biology, Institute of Cardiology, ul. Alpejska 42, Warszawa, 04-628, Poland;Department of Immunology, Center for Biostructure Research, Medical University of Warsaw, Warszawa, Poland;Department of Interventional Cardiology and Angiology, Institute of Cardiology, ul. Alpejska 42, Warszawa, 04-628, Poland;Department of Epidemiology, Cardiovascular Diseases Prevention and Promotion of Health, Institute of Cardiology, ul. Niemodlińska 33, Warszawa, 04-635, Poland;Department of Cardiomyopathies, Institute of Cardiology, ul. Alpejska 42, Warszawa, 04-628, Poland

关键词: Mutation;    PLN;    Phospholamban;    Genetic testing;    Hypertrophic cardiomyopathy;    Dilated cardiomyopathy;   

Others  :  1177683
DOI  :  10.1186/s12881-015-0167-0

 received in 2014-10-30, accepted in 2015-03-23,  发布年份 2015

【 摘 要 】

Background

In humans mutations in the PLN gene, encoding phospholamban - a regulator of sarcoplasmic reticulum calcium ATPase (SERCA), cause cardiomyopathy with prevalence depending on the population. Our purpose was to identify PLN mutations in Polish cardiomyopathy patients.

Methods

We studied 161 unrelated subjects referred for genetic testing for cardiomyopathies: 135 with dilated cardiomyopathy, 22 with hypertrophic cardiomyopathy and 4 with other cardiomyopathies. In 23 subjects multiple genes were sequenced by next generation sequencing and in all subjects PLN exons were analyzed by Sanger sequencing. Control group included 200 healthy subjects matched with patients for ethnicity, sex and age. Large deletions/insertions were screened by real time polymerase chain reaction.

Results

We detected three different heterozygous mutations in the PLN gene: a novel null c.9_10insA:(p.Val4Serfs*15) variant and two missense variants: c.25C > T:(p.Arg9Cys) and c.26G > T:(p.Arg9Leu). The (p.Val4Serfs*15) variant occurred in the patient with Wolff-Parkinson-White syndrome in whom the diagnosis of cardiomyopathy was not confirmed and his mother who had concentric left ventricular remodeling but normal left ventricular mass and function. We did not detect large deletions/insertions in PLN in cohort studied.

Conclusions

In Poland, similar to most populations, PLN mutations rarely cause cardiomyopathy. The 9^thPLN residue is apparently a mutation hot spot whereas a single dose of c.9_10insA, and likely other null PLN mutations, cause the disease only with low penetrance or are not pathogenic.

【 授权许可】

   
2015 Truszkowska et al.; licensee BioMed Central.

【 图 表 】

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