title: Evidence for exclusion of a mutation in NRAMP as the cause of familial disseminated atypical mycobacterial infection in a Maltese kindred.
abstract: In mice, susceptibility to intracellular infections in inbred strains is controlled by a single locus, Lsh/Ity/Bcg, and the gene responsible has been cloned and designated Nramp (Natural resistance associated macrophage protein). We have identified a group of related children who appear to have a single gene defect, inherited recessively, which results in increased susceptibility to myocabacterial infection. The immunological defect observed in the affected children resembles that in mice homozygous for the Lsh/Ity/Bcg susceptible allele. To test the hypothesis that a mutation in NRAMP is responsible for the immunodeficiency observed in the affected children, we have typed eight markers in the region of human 2q34-q37 where NRAMP, the human homologue of Nramp, maps. We have shown discordance with the defect in one family and the chromosomes in the three affected children have different haplotypes making it unlikely that inheritance of an ancestral mutation in the NRAMP gene is the cause of increased mycobacterial susceptibility in this group of children.
authors.affiliation: Department of Biochemistry and Molecular Genetics, St Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Newport
authors.forename: M
authors.initials: M
authors.lastname: Levin
authors.forename: J
authors.initials: J
authors.lastname: Blackwell
authors.forename: M A
authors.initials: MA
authors.lastname: Shaw
authors.forename: R
authors.initials: R
authors.lastname: Williamson
authors.forename: C
authors.initials: C
authors.lastname: Huxley
mesh_terms: D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D027682:Cation Transport Proteins; D002648:Child; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D004198:Disease Susceptibility / Q000662:veterinary; D005260:Female; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000662:veterinary; D033862:Iron-Binding Proteins; D008262:Macrophage Activation; D008297:Male; D008319:Malta; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009165:Mycobacterium Infections, Nontuberculous / Q000209:etiology* / Q000662:veterinary; D010375:Pedigree; D012376:Rodent Diseases / Q000235:genetics / Q000276:immunology; D013045:Species Specificity; D000099173:Natural Resistance-associated Macrophage Protein 1; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D033862:Iron-Binding Proteins; D008565:Membrane Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1; D000099236:Solute Carrier Family 11, Member 2