title: Manifestations and linkage analysis in X-linked autoimmunity-immunodeficiency syndrome.
abstract: The clinical findings of a kindred with an X-linked disorder are characterized by autoimmune polyendocrinopathy, enteropathy with villous atrophy, chronic dermatitis, and variable immunodeficiency. Linkage analysis was performed on 20 members of the affected kindred to determine the location of the responsible locus. Informative recombinations limited the region to an approximate 20 cM interval bordered by DXS1055 and DXS1196/DXS1050. Multipoint analysis generated a lod score >3 for the region contained between DXS8024 and DXS8031. The candidate region includes the Wiskott-Aldrich syndrome (WAS) locus. Evaluation of the Wiskott-Aldrich syndrome protein gene by single strand conformational analysis, heteroduplex analysis, and direct sequencing of the 12 exons in an affected male and two carrier females revealed no abnormalities. We conclude that this kindred has an X-linked disorder, distinct from WAS, that results in autoimmunity and variable immunodeficiency. The responsible locus maps to the pericentromeric region Xp11.23 to Xq21.1.
authors.affiliation: Department of Pediatrics, University of Virginia, Charlottesville, USA. pjf2d@virginia.edu
authors.forename: P J
authors.initials: PJ
authors.lastname: Ferguson
authors.forename: S H
authors.initials: SH
authors.lastname: Blanton
authors.forename: F T
authors.initials: FT
authors.lastname: Saulsbury
authors.forename: M J
authors.initials: MJ
authors.lastname: McDuffie
authors.forename: V
authors.initials: V
authors.lastname: Lemahieu
authors.forename: J M
authors.initials: JM
authors.lastname: Gastier
authors.forename: U
authors.initials: U
authors.lastname: Francke
authors.forename: S M
authors.initials: SM
authors.lastname: Borowitz
authors.forename: J L
authors.initials: JL
authors.lastname: Sutphen
authors.forename: T E
authors.initials: TE
authors.lastname: Kelly
mesh_terms: D015551:Autoimmunity; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D007223:Infant; D008297:Male; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000032:analysis / Q000235:genetics*; D012729:Sex Chromosome Aberrations / Q000175:diagnosis*; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics; D051316:Wiskott-Aldrich Syndrome Protein; D014960:X Chromosome / Q000235:genetics*
chemical_list: D011506:Proteins; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein