Patient with a 22q11.2 deletion with no overlap of the minimal DiGeorge syndrome critical region (MDGCR)

Abstract

The apparent lack of genotype/phenotype correlation in patients with the DiGeorge anomaly and velocardiofacial syndrome (DGA/VCFS; the "22q11 deletion syndrome") indicates a complex genetic condition. Most cases, whatever the phenotype, have a 1.5-3 Mb chromosomal deletion that includes the minimal DiGeorge critical region (MDGCR). Another potential critical region on 22q11 has been suggested based on two patients with distal deletions outside the MDGCR. We report on a patient with a VCFS phenotype who has a deletion, mapped by short tandem repeat polymorphic loci and fluorescence in situ hybridization analysis, distal to and not overlapping the MDGCR. This patient is deleted for several genes, including the T-box 1 gene (TBX1; a transcription regulator expressed early in embryogenesis) and catechol-O-methyltransferase (COMT; involved in neurotransmitter metabolism). We discuss the role these two genes may play in the clinical phenotype of the patient.

Transcriptional Regulation of Cardiac Development: Implications for Congenital Heart Disease and DiGeorge Syndrome

“…While animals homozygous for the 150-Kb deletion died early in gestation, heterozygous animals were without significant morphogenetic phenotypes. This is consistent with the recent identification of DGS patients with deletions completely outside the MDGCR (87).…”

A novel atypical 22q11.2 distal deletion in father and son

“…[8][9][10][11][12][13][14] These are either nested within the large 3 Mb typical deleted region, or they are distal to and do not overlap with it. The phenotype of patients with distal deletions not overlapping the minimal DiGeorge critical region seems to be indistinguishable from that of patients with the common large deletion.…”

“…7 However, to date seven patients have been reported with atypical deletions that show no overlap with this critical region. [8][9][10][11][12][13][14] These cases are extremely valuable as they may provide some insight into the underlying molecular mechanisms and may help to identify potential gene(s) involved.…”

Systematic assessment of atypical deletions reveals genotype-phenotype correlation in 22q11.2

“…[6][7][8] Furthermore, Kurahashi et al 9 investigated 100 patients with several fluorescent in situ hybridisation (FISH) probes from the 3 Mb region and detected a small distally nested deletion in one patient. A few patients with typical phenotype but normal results for the commonly used probes were further investigated and reported to have atypical nested deletions, [10][11][12][13][14] but also adjacent atypical distal deletions. 15 16 As both common and atypical deletions were shown to be mediated by several low copy repeats (LCR) within the region, 6 15 17 18 we suspected that, if investigated systematically, atypical deletions would be revealed to be more common than reported.…”