title: The gene responsible for autoimmune polyglandular syndrome type 1 maps to chromosome 21q22.3 in US patients.
abstract: Autoimmune polyglandular syndrome type 1 [APS-1] comprises multiple organ-specific autoimmunities such as acquired hypoparathyroidism and autoimmune Addison's disease, and a predisposition to certain infections such as chronic mucocutaneous candidiasis. An APS-1 candidate gene was assigned to chromosome 21q22.3 by linkage analyses in patients with APS-1 from Finland. To examine the influence of ethnic and geographic differences on the location of the candidate gene locus, we studied 24 US patients with APS-1 by microsatellite marker typing, using five microsatellite markers, D21S49, PFKL, D21S171, D21S1903 and CD18, selected from chromosome 21q22.3. By allelic association analyses, the frequencies of allele number 5 for D21S171 and allele number 8 for D21S1903 were significantly higher in the 24 patients with APS-1 than in 33 controls (33/48 vs. 31/66, P = 0.0207, X2 = 5.35; 12/48 vs. 7/66, P = 0.0418, X2 = 4.15 respectively). The frequency of homozygosity for allele number 5 of D21S171 was also significantly higher in the patients than in controls, 15/24 vs. 9/33 (P = 0.0078, X2 = 7.07). Maximum lod scores detected for the five markers in nine families (containing 15 of the patients with APS-1) were: 2.384 for D21S49, 3.144 for PFKL, 3.506 for D21S171, 4.329 for D21S1903, and 1.130 for CD18. These results confirm the linkage of the candidate APS-1 gene to 21q22.3 in US APS-1 patients, and suggest that the candidate gene is located near the D21S1903 marker. The demonstration of the location of the APS-1 candidate gene to 21q22.3 in an out-bred heterogeneous patient population should promote the physical mapping of the responsible gene.
authors.affiliation: Research Institute for Children, Harahan, LA 70123, USA.
authors.forename: Q Y
authors.initials: QY
authors.lastname: Chen
authors.forename: M S
authors.initials: MS
authors.lastname: Lan
authors.forename: J X
authors.initials: JX
authors.lastname: She
authors.forename: N K
authors.initials: NK
authors.lastname: Maclaren
mesh_terms: D000483:Alleles; D018912:Arabs / Q000235:genetics; D001327:Autoimmune Diseases / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D004700:Endocrine System Diseases / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D005006:Ethnicity / Q000235:genetics*; D005060:Europe / Q000208:ethnology; D005260:Female; D005387:Finland / Q000208:ethnology; D005602:France / Q000208:ethnology; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D013577:Syndrome; D014481:United States / Q000453:epidemiology