Genetic linkage of familial granulomatous inflammatory arthritis, skin rash, and uveitis to chromosome 16.
Blau syndrome (MIM 186580), first described in a large, three-generation kindred, is an autosomal, dominantly inherited disease characterized by multiorgan, tissue-specific inflammation. Its clinical phenotype includes granulomatous arthritis, skin rash, and uveitis and probably represents a subtype of a group of clinical entities referred to as "familial granulomatosis." It is the sole human model with recognizably Mendelian inheritance for a variety of multisystem inflammatory diseases affecting a significant percentage of the population. A genomewide search for the Blau susceptibility locus was undertaken after karyotypic analysis revealed no abnormalities. Sixty-two of the 74-member pedigree were genotyped with dinucleotide-repeat markers. Linkage analysis was performed under a dominant model of inheritance with reduced penetrance. The marker D16S298 gave a maximum LOD score of 3.75 at theta = .04, with two-point analysis. LOD scores for flanking markers were consistent and placed the Blau susceptibility locus within the 16p12-q21 interval.
Department of Biochemistry, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, USA.
G
G
Tromp
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H
Kuivaniemi
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S
Raphael
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L
Ala-Kokko
A
A
Christiano
E
E
Considine
R
R
Dhulipala
J
J
Hyland
A
A
Jokinen
S
S
Kivirikko
R
R
Korn
S
S
Madhatheri
S
S
McCarron
L
L
Pulkkinen
H
H
Punnett
K
K
Shimoya
L
L
Spotila
A
A
Tate
C J
CJ
Williams
D000293:Adolescent; D000328:Adult; D001168:Arthritis / Q000235:genetics*; D002648:Child; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16; D005260:Female; D008040:Genetic Linkage; D006099:Granuloma / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010375:Pedigree; D012871:Skin Diseases / Q000235:genetics*; D013577:Syndrome; D014605:Uveitis / Q000235:genetics*