Identification of a variant hotspot in "MYBPC3" and of a novel "CSRP3" autosomal recessive alteration in a cohort of Polish patients with hypertrophic cardiomyopathy

INTRODUCTION Hypertrophic cardiomyopathy (HCM) is a heart disorder caused by autosomal dominant alterations affecting both sarcomeric genes and other nonsarcomeric loci in a minority of cases. However, in some patients, the occurrence of the causal pathogenic variant or variants in homozygosity, com...

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Bibliographic Details
Published in:Polish Archives of Internal Medicine
Main Authors: Lipari, Martina, Wypasek, Ewa, Karpinski, Marek, Tomkiewicz-Pająk, Lidia, Laino, Luigi, Binni, Francesco, Giannarelli, Diana, Rubiś, Paweł, Petkow-Dimitrow, Paweł, Undas, Anetta, Grammatico, Paola, Bottillo, Irene
Format: Other/Unknown Material
Language:English
Published: 2020
Subjects:
CSRP3 human KO
hypertrophic cardiomyopathy
MYBPC3 founder mutation
Polish population
Iceland
Online Access:https://ruj.uj.edu.pl/xmlui/handle/item/257070
https://doi.org/10.20452/pamw.15130
https://www.mp.pl/paim/issue/article/15130
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Summary:INTRODUCTION Hypertrophic cardiomyopathy (HCM) is a heart disorder caused by autosomal dominant alterations affecting both sarcomeric genes and other nonsarcomeric loci in a minority of cases. However, in some patients, the occurrence of the causal pathogenic variant or variants in homozygosity, compound heterozygosity, or double heterozygosity has also been described. Most of the HCM pathogenic variants are missense and unique, but truncating mutations of the MYBPC3 gene have been reported as founder pathogenic variants in populations from Finland, France, Japan, Iceland, Italy, and the Netherlands. OBJECTIVES This study aimed to assess the genetic background of HCM in a cohort of Polish patients. PATIENTS AND METHODS Twenty‑nine Polish patients were analyzed by a next‑generation sequencing panel including 404 cardiovascular genes. RESULTS Pathogenic variants were found in 41% of the patients, with ultra‑rare MYBPC3 c.2541C>G (p.Tyr847Ter) mutation standing for a variant hotspot and correlating with a lower age at HCM diagnosis. Among the nonsarcomeric genes, the CSRP3 mutation was found in a single case carrying the novel c.364C>T (p.Arg122Ter) variant in homozygosity. With this finding, the total number of known HCM cases with human CSRP3 knockout cases has reached 3. CONCLUSIONS This report expands the mutational spectrum and the inheritance pattern of HCM.

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