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 mutationsReportar como inadecuado




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 - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Medical Genetics

, 16:21

Clinical-Molecular Genetics and Cytogenetics

Abstract

BackgroundIn 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.

MethodsWe 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.

ResultsWe 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.

ConclusionsIn Poland, similar to most populations, PLN mutations rarely cause cardiomyopathy. The 9PLN 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.

KeywordsDilated cardiomyopathy Hypertrophic cardiomyopathy Genetic testing Phospholamban PLN Mutation AbbreviationsDCMDilated cardiomyopathy

HCMHypertrophic cardiomyopathy

ICDImplantable cardioverter-defibrilator

LVEFLeft ventricular ejection fraction

nsVTNonsustained ventricular tachycardia

LVNCLeft ventricular non-compaction

SNVSingle nucleotide variation

VUSVariant of unknown significance

WPWWolf-Parkinson-White

Electronic supplementary materialThe online version of this article doi:10.1186-s12881-015-0167-0 contains supplementary material, which is available to authorized users.

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Autor: Grażyna T Truszkowska - Zofia T Bilińska - Joanna Kosińska - Justyna Śleszycka - Małgorzata Rydzanicz - Małgorzata S

Fuente: https://link.springer.com/







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