Patient with a 22q11.2 deletion with no overlap of the minimal DiGeorge syndrome critical region (MDGCR).
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.
McQuade
L
L
VCFS Research Group, Clinical Sciences, Royal Alexandra Hospital for Children, Parramatta, New South Wales, Australia.
Christodoulou
J
J
Budarf
M
M
Sachdev
R
R
Wilson
M
M
Emanuel
B
B
Colley
A
A
D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics; D002869:Chromosome Aberrations / Q000175:diagnosis / Q000235:genetics*; D002872:Chromosome Deletion; D025063:Chromosome Disorders; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004062:DiGeorge Syndrome / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006239:Haplotypes; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009679:Nuclear Family; D010641:Phenotype; D020161:Physical Chromosome Mapping; D013577:Syndrome; D020825:T-Box Domain Proteins; D020080:Tandem Repeat Sequences / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
D004268:DNA-Binding Proteins; D020825:T-Box Domain Proteins; C108625:TBX1 protein, human; D014157:Transcription Factors; D002394:Catechol O-Methyltransferase