Mutations in the ABCG8 gene are associated with sitosterolaemia in the homozygous form and xanthelasmas in the heterozygous form.

Sitosterol is the most abundant plant sterol found in our diet. Sitosterolemia (OMIM 210250), also known as phytosterolaemia, is a rare autosomal recessive disease caused by the inability to efficiently excrete plant sterol, and is characterized by cutaneous xanthomas and accelerated atherosclerosis. Sitosterolaemia is caused by homozygous or compound heterozygous mutations in either ABCG5 or ABCG8 (both on chromosome 2p21), which encode the sterol efflux transporter ABCG5 (sterolin-1) and ABCG8 (sterolin-2), respectively. To investigate a Tunisian family with several members who manifested with generalized cutaneous xanthomas, whereas others had only isolated xanthelasmas. Genetic analysis was performed based on exome sequencing of DNA obtained from five affected individuals and one unaffected individual from a Tunisian family. RESULTS: A novel mutation in the ABCG8 gene, designated c.965-1G>C, was identified by exome sequencing in the members of this family. The homozygous form was associated with generalized cutaneous xanthomatosis while the heterozygous form was linked to isolated xanthelasmas. Our results indicate a gene dosage effect of ABCG8 and suggest that individuals at risk should be followed closely.