CCL

Összesen 1 találat.
#/oldal:
Részletezés:
Rendezés:

1.

001-es BibID:BIBFORM099807
035-os BibID:(cikkazonosító)635480
Első szerző:Zodanu, Gloria Kafui Esi
Cím:Systemic Screening for 22q11.2 Copy Number Variations in Hungarian Pediatric and Adult Patients With Congenital Heart Diseases Identified Rare Pathogenic Patterns in the Region / Zodanu Gloria Kafui Esi, Oszlánczi Mónika, Havasi Kálmán, Kalapos Anita, Rácz Gergely, Katona Márta, Ujfalusi Anikó, Nagy Orsolya, Széll Márta, Nagy Dóra
Dátum:2021
ISSN:1664-8021
Megjegyzések:Congenital heart defects (CHD) are the most common developmental abnormalities, affecting approximately 0.9% of livebirths. Genetic factors, including copy number variations (CNVs), play an important role in their development. The most common CNVs are found on chromosome 22q11.2. The genomic instability of this region, caused by the eight low copy repeats (LCR A-H), may result in several recurrent and/or rare microdeletions and duplications, including the most common, ?3 Mb large LCR A-D deletion (classical 22q.11.2 deletion syndrome). We aimed to screen 22q11.2 CNVs in a large Hungarian pediatric and adult CHD cohort, regardless of the type of their CHDs. All the enrolled participants were cardiologically diagnosed with non-syndromic CHDs. A combination of multiplex ligation-dependent probe amplification (MLPA), chromosomal microarray analysis and droplet digital PCR methods were used to comprehensively assess the detected 22q11.2 CNVs in 212 CHD-patients. Additionally, capillary sequencing was performed to detect variants in the TBX1 gene, a cardinal gene located in 22q11.2. Pathogenic CNVs were detected in 5.2% (11/212), VUS in 0.9% and benign CNVs in 1.8% of the overall CHD cohort. In patients with tetralogy of Fallot the rate of pathogenic CNVs was 17% (5/30). Fifty-four percent of all CNVs were typical proximal deletions (LCR A-D). However, nested (LCR A-B) and central deletions (LCR C-D), proximal (LCR A-D) and distal duplications (LCR D-E, LCR D-H, LCR E-H, LCR F-H) and rare combinations of deletions and duplications were also identified. Segregation analysis detected familial occurrence in 18% (2/11) of the pathogenic variants. Based on in-depth clinical information, a detailed phenotype-genotype comparison was performed. No pathogenic variant was identified in the TBX1 gene. Our findings confirmed the previously described large phenotypic diversity in the 22q11.2 CNVs. MLPA proved to be a highly efficient genetic screening method for our CHD-cohort. Our results highlight the necessity for large-scale genetic screening of CHD-patients and the importance of early genetic diagnosis in their clinical management.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
22q11.2 deletion syndrome
TBX1 gene
chromosomal microarray analysis
copy number variations
droplet digital PCR
multiplex ligation-dependent probe amplification
syndromic and non-syndromic congenital heart defects
Megjelenés:Frontiers in Genetics. - 12 (2021), p. 1-11. -
További szerzők:Oszlánczi Mónika Havasi Kálmán Kalapos Anita Rácz Gergely Katona Márta Ujfalusi Anikó (1968-) (gyermekorvos, laboratóriumi szakorvos) Nagy Orsolya (1990-) (PhD hallgató) Széll Márta Nagy Dóra
Pályázati támogatás:GINOP-2.3.2-15-2016-00039
GINOP
Hungarian Scientific Research Fund (Grant No. 5S441-A202)
Egyéb
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Rekordok letöltése1