Clinical-genetic analysis of selected genes involved in the development of the human skeleton in 128 Czech patients with suspected congenital skeletal abnormalities

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00098892%3A_____%2F24%3A10158152" target="_blank" >RIV/00098892:_____/24:10158152 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15110/24:73621312 RIV/61989592:15640/24:73621312

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0378111923007229?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0378111923007229?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.gene.2023.147881" target="_blank" >10.1016/j.gene.2023.147881</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Clinical-genetic analysis of selected genes involved in the development of the human skeleton in 128 Czech patients with suspected congenital skeletal abnormalities

Popis výsledku v původním jazyce

Background: Congenital skeletal abnormalities are a heterogeneous group of diseases most commonly associated with small or disproportionate growth, cranial and facial dysmorphisms, delayed bone maturation, etc. Nonetheless, no detailed genotype-phenotype correlation in patients with specific genetic variants is readily available. Ergo, this study focuses on the analysis of patient phenotypes with candidate variants in genes involved in bone growth as detected by molecular genetic analysis. Methods: In this study we used molecular genetic methods to analyse the ACAN, COL2A1, FGFR3, IGFALS, IGF1, IGF1R, GHR, NPR2, STAT5B and SHOX genes in 128 Czech children with suspected congenital skeletal abnormalities. Pathogenic variants and variants of unclear clinical significance were identified and we compared their frequency in this study cohort to the European non-Finnish population. Furthermore, a prediction tool was utilised to determine their possible impact on the final protein. All clinical patient data was obtained during pretest genetic counselling. Results: Pathogenic variants were identified in the FGFR3, GHR, COL2A1 and SHOX genes in a total of six patients. Furthermore, we identified 23 variants with unclear clinical significance and high allelic frequency in this cohort of patients with skeletal abnormalities. Five of them have not yet been reported in the scientific literature. Conclusion: Congenital skeletal abnormalities may lead to a number of musculoskeletal, neurological, cardiovascular problems. Knowledge of specific pathogenic variants may help us in therapeutic procedures.

Název v anglickém jazyce

Clinical-genetic analysis of selected genes involved in the development of the human skeleton in 128 Czech patients with suspected congenital skeletal abnormalities

Popis výsledku anglicky

Background: Congenital skeletal abnormalities are a heterogeneous group of diseases most commonly associated with small or disproportionate growth, cranial and facial dysmorphisms, delayed bone maturation, etc. Nonetheless, no detailed genotype-phenotype correlation in patients with specific genetic variants is readily available. Ergo, this study focuses on the analysis of patient phenotypes with candidate variants in genes involved in bone growth as detected by molecular genetic analysis. Methods: In this study we used molecular genetic methods to analyse the ACAN, COL2A1, FGFR3, IGFALS, IGF1, IGF1R, GHR, NPR2, STAT5B and SHOX genes in 128 Czech children with suspected congenital skeletal abnormalities. Pathogenic variants and variants of unclear clinical significance were identified and we compared their frequency in this study cohort to the European non-Finnish population. Furthermore, a prediction tool was utilised to determine their possible impact on the final protein. All clinical patient data was obtained during pretest genetic counselling. Results: Pathogenic variants were identified in the FGFR3, GHR, COL2A1 and SHOX genes in a total of six patients. Furthermore, we identified 23 variants with unclear clinical significance and high allelic frequency in this cohort of patients with skeletal abnormalities. Five of them have not yet been reported in the scientific literature. Conclusion: Congenital skeletal abnormalities may lead to a number of musculoskeletal, neurological, cardiovascular problems. Knowledge of specific pathogenic variants may help us in therapeutic procedures.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30101 - Human genetics

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Gene

ISSN

0378-1119

e-ISSN

1879-0038

Svazek periodika

892

Číslo periodika v rámci svazku

January

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

14

Strana od-do

147881

Kód UT WoS článku

001098835600001

EID výsledku v databázi Scopus

2-s2.0-85174042691