Familial antiphospholipid antibody syndrome - Criteria for disease and evidence for autosomal dominant inheritance

Objective. To develop diagnostic criteria for a familial form of antiphosph olipid antibody syndrome (APS), identify families with >1 affected member, examine possible modes of inheritance, and determine linkage to potential c andidate genes. Methods. Family members of probands with primary APS were analyzed for clin ical and laboratory abnormalities associated with APS. Families with greate r than or equal to 2 affected members were analyzed by segregation analysis and typed for candidate genetic markers. Results. Seven families were identified. Thirty of 101 family members met d iagnostic criteria for APS. Segregation studies rejected both environmental and autosomal recessive models, and the data were best fit by either a dom inant or codominant model. Linkage analysis showed independent segregation of APS and several candidate genes. Conclusion. Clinical and laboratory criteria are essential to identify the spectrum of disease associated with APS. We believe a set of criteria was d eveloped that can precisely define affected family members with APS. Modeli ng studies utilizing these criteria strongly support a genetic basis for di sease in families with APS and suggest that a susceptibility gene is inheri ted in an autosomal dominant pattern. However, in these families, APS was n ot linked with HLA, Fas, or other candidate genes, including beta(2)-glycop rotein I, HLA, T cell receptor beta chain, Ig heavy chain, antithrombin III , Fas ligand, factor V, complement factor H, IgK, and Fas.