LDLR gene rearrangements in Czech FH patients likely arise from one mutational event

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F24%3A00079457" target="_blank" >RIV/65269705:_____/24:00079457 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14310/24:00135521 RIV/00209775:_____/24:N0000015

Result on the web

<a href="https://lipidworld.biomedcentral.com/articles/10.1186/s12944-024-02013-3" target="_blank" >https://lipidworld.biomedcentral.com/articles/10.1186/s12944-024-02013-3</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s12944-024-02013-3" target="_blank" >10.1186/s12944-024-02013-3</a>

Result language

angličtina

Original language name

LDLR gene rearrangements in Czech FH patients likely arise from one mutational event

Original language description

Background Large deletions and duplications within the low-density lipoprotein receptor (LDLR) gene make up approximately 10% of LDLR pathogenic variants found in Czech patients with familial hypercholesterolemia. The goal of this study was to test the hypothesis that all probands with each rearrangement share identical breakpoints inherited from a common ancestor and to determine the role of Alu repetitive elements in the generation of these rearrangements. Methods The breakpoint sequence was determined by PCR amplification and Sanger sequencing. To confirm the breakpoint position, an NGS analysis was performed. Haplotype analysis of common LDLR variants was performed using PCR and Sanger sequencing. Results The breakpoints of 8 rearrangements within the LDLR gene were analysed, including the four most common LDLR rearrangements in the Czech population (number of probands ranging from 8 to 28), and four less common rearrangements (1-4 probands). Probands with a specific rearrangement shared identical breakpoint positions and haplotypes associated with the rearrangement, suggesting a shared origin from a common ancestor. All breakpoints except for one were located inside an Alu element. In 6 out of 8 breakpoints, there was high homology (&gt;= 70%) between the two Alu repeats in which the break occurred. Conclusions The most common rearrangements of the LDLR gene in the Czech population likely arose from one mutational event. Alu elements likely played a role in the generation of the majority of rearrangements inside the LDLR gene.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Lipids in Health and Disease

ISSN

1476-511X

e-ISSN

1476-511X

Volume of the periodical

23

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

11

Pages from-to

36

UT code for WoS article

001156563100001

EID of the result in the Scopus database

2-s2.0-85183687769