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

J 2024

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

KONEČNÁ, Kateřina; Petra ZAPLETALOVA; Tomáš FREIBERGER a Lukáš TICHÝ

Základní údaje

Originální název

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

Autoři

KONEČNÁ, Kateřina ; Petra ZAPLETALOVA; Tomáš FREIBERGER a Lukáš TICHÝ

Vydání

LIPIDS IN HEALTH AND DISEASE, LONDON, BMC, 2024, 1476-511X

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30201 Cardiac and Cardiovascular systems

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.200

Kód RIV

RIV/00216224:14310/24:00135521

Organizační jednotka

Přírodovědecká fakulta

DOI

https://doi.org/10.1186/s12944-024-02013-3

UT WoS

001156563100001

EID Scopus

2-s2.0-85183687769

Klíčová slova anglicky

Low-density lipoprotein receptor; LDLR; Familial hypercholesterolemia; Alu; Rearrangements; Breakpoints

Štítky

14110114, 143160, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 3. 3. 2025 16:10, Mgr. Marie Novosadová Šípková, DiS.

Anotace

V originále

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 (>= 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.

Návaznosti

LX22NPO5104, projekt VaV

Název: Národní institut pro výzkum metabolických a kardiovaskulárních onemocnění (Akronym: CarDia)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní institut pro léčbu metabolických a kardiovaskulárních onemocnění, 5.1 EXCELES

Přiložené soubory

LDLR_gene_rearrangements_in_Czech_FH_patients_likely_arise_from_one_mutational_event.pdf

Citovat

KONEČNÁ, Kateřina; Petra ZAPLETALOVA; Tomáš FREIBERGER a Lukáš TICHÝ. LDLR gene rearrangements in Czech FH patients likely arise from one mutational event. LIPIDS IN HEALTH AND DISEASE. LONDON: BMC, 2024, roč. 23, č. 1, s. 1-11. ISSN 1476-511X. Dostupné z: https://doi.org/10.1186/s12944-024-02013-3.

@article{2374288,
   author = {Konečná, Kateřina and Zapletalova, Petra and Freiberger, Tomáš and Tichý, Lukáš},
   article_location = {LONDON},
   article_number = {1},
   doi = {https://doi.org/10.1186/s12944-024-02013-3},
   keywords = {Low-density lipoprotein receptor; LDLR; Familial hypercholesterolemia; Alu; Rearrangements; Breakpoints},
   language = {eng},
   issn = {1476-511X},
   journal = {LIPIDS IN HEALTH AND DISEASE},
   title = {LDLR gene rearrangements in Czech FH patients likely arise from one mutational event},
   url = {https://lipidworld.biomedcentral.com/articles/10.1186/s12944-024-02013-3},
   volume = {23},
   year = {2024}
}

TY  - JOUR
ID  - 2374288
AU  - Konečná, Kateřina - Zapletalova, Petra - Freiberger, Tomáš - Tichý, Lukáš
PY  - 2024
TI  - LDLR gene rearrangements in Czech FH patients likely arise from one mutational event
JF  - LIPIDS IN HEALTH AND DISEASE
VL  - 23
IS  - 1
SP  - 1-11
EP  - 1-11
PB  - BMC
SN  - 1476511X
KW  - Low-density lipoprotein receptor
KW  - LDLR
KW  - Familial hypercholesterolemia
KW  - Alu
KW  - Rearrangements
KW  - Breakpoints
UR  - https://lipidworld.biomedcentral.com/articles/10.1186/s12944-024-02013-3
N2  - 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 (>= 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.
ER  -

KONEČNÁ, Kateřina; Petra ZAPLETALOVA; Tomáš FREIBERGER a Lukáš TICHÝ. LDLR gene rearrangements in Czech FH patients likely arise from one mutational event. \textit{LIPIDS IN HEALTH AND DISEASE}. LONDON: BMC, 2024, roč.~23, č.~1, s.~1-11. ISSN~1476-511X. Dostupné z: https://doi.org/10.1186/s12944-024-02013-3.

Přehled o publikaci