A rare coincidence of sitosterolemia and familial mediterranean fever identified by whole exome sequencing

Whole exome sequencing (wes) technologies have accelerated genetic studies of mendelian disorders,yielding approximately 30% diagnostic success. we encountered a 13-year-old japanese female initially diagnosed with familial hypercholesterolemia on the basis of clinical manifestations of severe hypercholesterolemia (initial ldl cholesterol =609 mg/dl at the age of one) and systemic intertriginous xanthomas with histories of recurrent self-limiting episodes of fever and arthritis. both her phenotypes seemed to co-segregate in a recessive manner. we performed wes on this patient,who was considered a proband. among 206,430 variants found in this individual,we found 18,220 nonsense,missense,or splice site variants,of which 3,087 were rare (minor allele frequency ≤ 0.01 or not reported) in 1000 genome (asian population). filtering by assuming a recessive pattern of inheritance with the use of an in silico annotation prediction tool,we successfully narrowed down the candidates to the compound heterozygous mutations in the abcg5 gene (c.1256g>a or p.arg419his/ c.1763-1g>a [splice acceptor site]) and to the double-compound heterozygous mutations in the mefv gene (c.329t>c/c or p.leu110pro/c.442g>c/c or p.glu148val). the patient was genetically diagnosed with sitosterolemia and familial mediterranean fever using wes for the first time. such a comprehensive approach is useful for identifying causative mutations for multiple unrelated inheritable diseases. © 2016,japan atherosclerosis society. all rights reserved.