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

Abstract

Objective. To develop diagnostic criteria for a familial form of antiphospholipid antibody syndrome (APS), identify families with >1 affected member, examine possible modes of inheritance, and determine linkage to potential candidate genes.Methods. Family members of probands with primary APS were analyzed for clinical and laboratory abnormalities associated with APS. Families with >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 diagnostic criteria for APS.Segregation studies rejected both environmental and autosomal recessive models, and the data were best fit by either a dominant 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 developed that can precisely define affected family members with APS. Modeling studies utilizing these criteria strongly support a genetic basis for disease in families with APS and suggest that a susceptibility gene is inherited in an autosomal dominant pattern. However, in these families, APS was not linked with HLA, Fas, or other candidate genes, including ␤ 2 -glycoprotein I, HLA, T cell receptor ␤ chain, Ig heavy chain, antithrombin III, Fas ligand, factor V, complement factor H, IgK, and Fas.

Detection of antibody-mediated reduction of annexin A5 anticoagulant activity in plasmas of patients with the antiphospholipid syndrome

“…Lupus anticoagulants were identified using the criteria proposed by the Subcommittee on Lupus Anticoagulants/Antiphospholipid Antibodies of the International Society of Thrombosis and Haemostasis, 19 as previously described. 20 Anticardiolipin antibody IgG and IgM levels were determined by enzyme-linked immunosorbent assay using an in-house test developed in the Clinical Immunology lab of Duke University Medical Center, as described by Loizou et al 21 Antiphospholipid antibody testing was performed on one or more occasions at a time when the patient was clinically stable. Repeat anticardiolipin antibody analysis was performed on all patient samples.…”

Familial antiphospholipid syndrome presenting as bivessel arterial occlusion in a 17-year-old girl

“…There have been conducted statistical analyses on families with APS clusterings, and these have shown a possible autosomal dominant pattern of inheritance of aPL antibody production and associated clinical manifestations [8]. Still, no firm gene association has been identified for APS yet, in part because of the rarity of multiplex families to study and because of the possibility of another familial cause of thrombotic disease [9].…”

A simple and accurate method for determination of microsatellite total allele content differences between DNA pools

“…DNA pooling and genotyping DNA was prepared from human buccal cell samples as described (Goel et al 1999). All samples were then quantified in microtiter trays by using the PicoGreen fluorescence assay (Molecular Probes), as suggested by the manufacturers, and the FMBIO II fluorescence reader (Hitachi).…”