An immune defect causing dominant chronic mucocutaneous candidiasis and thyroid disease maps to chromosome 2p in a single family.
We describe a large family in which a combination of chronic mucocutaneous candidiasis (fungal infections of the skin, nails, and mucous membranes) and thyroid disease segregate as an autosomal dominant trait with reduced penetrance. The family includes (a) four members with both candidiasis and thyroid disease, (b) five members, including one pair of phenotype-concordant MZ twins, with candidiasis only, and (c) three members with thyroid disease only. A whole-genome scan using DNA samples from 20 members of the family identified a candidate linkage region on chromosome 2p. By sampling additional individuals and genotyping supplementary markers, we established linkage to a region of approximately 15 cM bounded by D2S367 and D2S2240 and including seven adjacent markers consistent with linkage. With a penetrance estimate of.8, which was based on pedigree and affected status, the peak two-point LOD score was 3.70 with marker D2S2328, and the peak three-point LOD score was 3.82. This is the first linkage assignment of a dominant locus for mucocutaneous candidiasis.
Atkinson
T P
TP
Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.
Schäffer
A A
AA
Grimbacher
B
B
Schroeder
H W
HW
Woellner
C
C
Zerbe
C S
CS
Puck
J M
JM
D000328:Adult; D000483:Alleles; D002178:Candidiasis, Chronic Mucocutaneous / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D002648:Child; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D005799:Genes, Dominant / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D010375:Pedigree; D019683:Penetrance; D012882:Skin Tests; D013959:Thyroid Diseases / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology
D005819:Genetic Markers