title: Germ-line mosaicism simulates genetic heterogeneity in Wiskott-Aldrich syndrome.
abstract: The Wiskott-Aldrich syndrome (IMD2) is an X-linked recessive immunodeficiency. Initial linkage studies mapped the disease locus on the proximal short arm of the X chromosome, a localization which was further refined to the interval framed by DXS7 and DXS14. We have recently shown that a novel hypervariable locus, DXS255, is very closely linked to the disease gene and is likely to be, at present, the marker closest to the disease gene. The analysis of one family, however, displayed conflicting linkage results, as all of the informative markers situated in the Xp11-q22 region appeared to recombine with the disease locus in two "phase-known" meioses. We have shown by X-inactivation studies that the segregation of the disease through three obligate carrier females in this family originates from a grandpaternal mosaicism, which accounts for the apparent recombinations. This shows that germ-line mosaicism can simulate genetic heterogeneity in linkage studies.
authors.affiliation: Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Unité 184 de l'INSERM, Faculté de Médecine, Strasbourg.
authors.forename: B
authors.initials: B
authors.lastname: Arveiler
authors.forename: G
authors.initials: G
authors.lastname: de Saint-Basile
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: C
authors.initials: C
authors.lastname: Griscelli
authors.forename: J L
authors.initials: JL
authors.lastname: Mandel
mesh_terms: D015139:Blotting, Southern; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D008040:Genetic Linkage; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D008297:Male; D008970:Molecular Weight; D009030:Mosaicism / Q000235:genetics*; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics*; D014960:X Chromosome
chemical_list: D004247:DNA