An exploratory study of predisposing genetic factors for DiGeorge/velocardiofacial syndrome
Vergés, Laia (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Vidal, Francesca (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Geán, Esther (Hospital Sant Joan de Déu (Manresa))
Alemany-Schmidt, Alexandra (Hospital Universitari Son Espases (Palma de Mallorca, Balears))
Oliver Bonet, Maria (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Blanco, Joan (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)

Date:	2017
Abstract:	DiGeorge/velocardiofacial syndrome (DGS/VCFS) is a disorder caused by a 22q11. 2 deletion mediated by non-allelic homologous recombination (NAHR) between low-copy repeats (LCRs). We have evaluated the role of LCR22 genomic architecture and PRDM9 variants as DGS/VCFS predisposing factors. We applied FISH using fosmid probes on chromatin fibers to analyze the number of tandem repeat blocks in LCR22 in two DGS/VCFS fathers-of-origin with proven 22q11. 2 NAHR susceptibility. Results revealed copy number variations (CNVs) of L9 and K3 fosmids in these individuals compared to controls. The total number of L9 and K3 copies was also characterized using droplet digital PCR (ddPCR). Although we were unable to confirm variations, we detected an additional L9 amplicon corresponding to a pseudogene. Moreover, none of the eight DGS/VCFS parents-of-origin was heterozygote for the inv(22)(q11. 2) haplotype. PRDM9 sequencing showed equivalent allelic distributions between DGS/VCFS parents-oforigin and controls, although a new PRDM9 allele (L50) was identified in one case. Our results support the hypothesis that LCR22s variations influences 22q11. 2 NAHR events, however further studies are needed to confirm this association and clarify the contribution of pseudogenes and rare PDRM9 alleles to NAHR susceptibility.
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Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Scientific reports, Vol. 7 (2017) , art. 40031, ISSN 2045-2322

DOI: 10.1038/srep40031
PMID: 28059126

11 p, 1.2 MB

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