Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
5-Year Impact Factor – 2.2
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Index Copernicus  – 161.11; MNiSW – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2007, vol. 16, nr 6, November-December, p. 717–723

Publication type: editorial article

Language: English

New Bacterial Artificial Chromosome and Commercial FISH Probes for the 22q11.2 Region in Patients with Congenital Heart Defect and with Phenotype Resembling DiGeorge and Velocardiofacial Syndromes

Badania FISH z użyciem nowych sztucznych chromosomów bakteryjnych oraz komercyjnych sond dla regionu 22q11.2 u pacjentów z wrodzoną wadą serca oraz fenotypem zespołu DiGeorge’a oraz zespołu podniebienno−sercowo−twarzowego

Robert Śmigiel1,, Małgorzata Piotrowicz2,, Izabela Łaczmańska1,, Izabela Makowska1,, Anna Błońska3,, Kristina Hoffmann4,, Lucjusz Jakubowski2,, Nikolaus Blin4,, Maria M. Sąsiadek1,

1 Department of Genetics, Silesian Piasts University of Medicine in Wrocław, Poland

2 Department of Genetics, Polish Mother’s Memorial Hospital Research Institute, Łódź, Poland

3 Department of Pathophysiology, Silesian Piasts University of Medicine in Wrocław, Poland

4 Department of Molecular Genetics, Institute of Human Genetics, University of Tuebingen, Tuebingen, Germany

Abstract

Background. The majority of patients with DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS) have a microdeletion in 22q11.2. The minimal DiGeorge critical region (MDGCR) has been narrowed down to 250 kb using FISH analysis. The construction of bacterial artificial contigs is an essential step towards the identification of deletions of smaller size.
Objectives. A set of bacterial artificial chromosomes (BACs) was used in a FISH assay in patients with congenital heart defect and phenotype resembling DGS/VCFS to determine new, specific, deleted regions not encompassed by commercial probes.
Material and Methods. The study group comprised 69 patients with congenital malformations, including heart defects and dysmorphic features. The patients were divided into three subgroups. Group I comprised patients diagnosed with DGS/VCF syndrome by the detection of a 22q11.2 deletion using FISH applying the commercial probes TUPLE1 and N25. All the patients in this group also had a FISH study with seven BAC probes (115F6, 678G6, 770H11, 201C11, 919E7, 219G6, 431E9) comprising the critical region 22q11.2. Group II was made up of patients with clinical features of DGS/VCFS but without a deletion detected by FISH using the commercial FISH probes. FISH with BAC probes was also performed in this group. Group III was patients with clinical features suggesting DGS/VCFS with no deletion detected by the TUPLE1 and N25 probes. FISH with the BAC probes was not performed in the group.
Results. Within group I, deletions in the regions for BACs 770H11, 201C11, 919E7, 219G6, and 431E9 were detected in all 14 children with DGS/VCFS. FISH study with the 115F6 and 678G6 probes revealed the correct two signals in all patients of group I. No deletions were detected by any of the seven BACs tested in group II involving the patients with clinical DGS/VCFS features, nor was a deletion detected by the commercial probes. The clinical symptoms of the patients of the three clinically heterogeneous groups with diagnosed and suspected DGS/VCFS were compared. Palate insufficiency, hypocalcemia, and recurrent infections were significantly more frequent in patients with a 22q11.2 microdeletion confirmed cytogenetically by FISH.
Conclusion. These results strongly suggest that strict diagnostic criteria for DGS/VCFS are needed.

Key words

DiGeorge syndrome, velocardiofacial syndrome, phenotype, FISH, microdeletion

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