title: Autosomal recessive chronic granulomatous disease caused by deletion at a dinucleotide repeat.
abstract: Chronic granulomatous disease (CGD) is a rare inherited condition rendering neutrophils incapable of killing invading pathogens. This condition is due to the failure of a multicomponent microbicidal oxidase that normally yields a low-midpoint-potential b cytochrome (cytochrome b245). Although defects in the X chromosome-linked cytochrome account for the majority of CGD patients, as many as 30% of CGD cases are due to an autosomal recessive disease. Of these, greater than 90% have been shown to be defective in the synthesis of a 47-kDa cytosolic component of the oxidase. We demonstrate here in three unrelated cases of autosomal recessive CGD that the identical underlying molecular lesion is a dinucleotide deletion at a GTGT tandem repeat, corresponding to the acceptor site of the first intron-exon junction. Slippage of the DNA duplex at this site may contribute to the high frequency of defects in this gene.
authors.affiliation: Department of Medicine, Rayne Institute, University College London, United Kingdom.
authors.forename: C M
authors.initials: CM
authors.lastname: Casimir
authors.forename: H N
authors.initials: HN
authors.lastname: Bu-Ghanim
authors.forename: A R
authors.initials: AR
authors.lastname: Rodaway
authors.forename: D L
authors.initials: DL
authors.lastname: Bentley
authors.forename: P
authors.initials: P
authors.lastname: Rowe
authors.forename: A W
authors.initials: AW
authors.lastname: Segal
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D002872:Chromosome Deletion; D003573:Cytochrome b Group / Q000235:genetics*; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D015226:Dinucleoside Phosphates / Q000032:analysis*; D005808:Genes, Recessive; D006105:Granulomatous Disease, Chronic / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D012016:Reference Values; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D014960:X Chromosome
chemical_list: D003573:Cytochrome b Group; D015226:Dinucleoside Phosphates; D012333:RNA, Messenger; D004247:DNA