Autoimmune Disease, Susceptibility To, 6

A number sign (#) is used with this entry because this form of susceptibility to autoimmune disease (AIS6) is caused by mutations in the gene encoding sialic acid acetylesterase (SIAE; 610079).

For a discussion of autoimmunity, see 109100.

Clinical Features

Surolia et al. (2010) identified heterozygous loss-of-function mutations (e.g., T312M; 610079.0001) and a homozygous defective polymorphic variant (M89V; 610079.0003) in the SIAE gene in 24 of 923 individuals of European origin with relatively common autoimmune diseases and in 2 of 648 controls of European origin (see MOLECULAR GENETICS). The autoimmune diseases found in individuals with SIAE mutations included juvenile idiopathic arthritis, rheumatoid arthritis (see 180300), multiple sclerosis (see 126200), Sjogren syndrome (see 270150), systemic lupus erythematosus (see 152700), type I diabetes (see 222100), ulcerative colitis (see 266600), and Crohn disease (see 266600).

Mapping

AIS6 is caused by mutations in the SIAE gene, which was mapped to chromosome 11q24 by Zhu et al. (2004).

Molecular Genetics

Surolia et al. (2010) identified heterozygous loss-of-function germline rare variants (e.g., T312M; 610079.0001) and a homozygous defective polymorphic variant (M89V; 610079.0003) in the SIAE gene in 24 of 923 individuals of European origin with relatively common autoimmune disorders and in 2 of 648 controls of European origin. All heterozygous loss-of-function SIAE mutations tested functioned in a dominant-negative manner. The homozygous secretion-defective polymorphic variant M89V was catalytically active, could not function in a dominant-negative manner, and was present in 8 individuals with autoimmune disease, but in no controls. The odds ratio for inheriting defective SIAE alleles was 8.6 in all individuals with autoimmune disease (95% confidence interval (CI) = 2.03-36.62; P = 0.0002), 8.3 in individuals with rheumatoid arthritis (see 180300) (95% CI = 1.69-40.87; P = 0.0056), and 7.9 in individuals with type I diabetes (see 222100) (95% CI = 1.58-39.30; P = 0.0075). Surolia et al. (2010) concluded that defective rare and polymorphic SIAE variants play a role in susceptibility to relatively common autoimmune diseases.