title: Isolation of a gene encoding an integral membrane protein from the vicinity of a balanced translocation breakpoint associated with DiGeorge syndrome.
abstract: Deletions within 22q11 have been associated with a wide variety of birth defects embraced by the acronym CATCH22 and including the DiGeorge syndrome, Shprintzen syndrome (velocardiofacial syndrome) and congenital heart disease. It is not known how many genes contribute to this phenotype. Previous studies have shown that a balanced translocation disrupts sequences within the shortest region of deletion overlap for DiGeorge syndrome. A P1 clone was isolated which spans this breakpoint and used to isolate a cDNA encoding a transmembrane protein expressed in a wide variety of tissues. This gene (called IDD) is not disrupted by the translocation, but maps within 10 kb of the breakpoint. Mutation analysis of five affected cases with no previously identified chromosome 22 deletion was negative, but a potential protein polymorphism was discovered. No deletions or rearrangements were detected in these patients following analysis with markers closely flanking the breakpoint, data which emphasize that large (i.e. over 1 Mb) interstitial deletions are the rule in DiGeorge syndrome. The proximity of IDD to the balanced translocation breakpoint and its position within the shortest region of deletion overlap indicate that this gene may have a role, along with other genes, in the CATCH22 haploinsufficiency syndromes.
authors.affiliation: Molecular Medicine Unit, Institute of Child Health, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Wadey
authors.forename: S
authors.initials: S
authors.lastname: Daw
authors.forename: C
authors.initials: C
authors.lastname: Taylor
authors.forename: U
authors.initials: U
authors.lastname: Atif
authors.forename: S
authors.initials: S
authors.lastname: Kamath
authors.forename: S
authors.initials: S
authors.lastname: Halford
authors.forename: H
authors.initials: H
authors.lastname: O'Donnell
authors.forename: D
authors.initials: D
authors.lastname: Wilson
authors.forename: J
authors.initials: J
authors.lastname: Goodship
authors.forename: J
authors.initials: J
authors.lastname: Burn
mesh_terms: D000595:Amino Acid Sequence; D017101:Bacteriophage P1; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22; D018076:DNA, Complementary; D004062:DiGeorge Syndrome / Q000235:genetics*; D005260:Female; D015723:Gene Library; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D018076:DNA, Complementary; D008565:Membrane Proteins