A Rare Coincidence of Sitosterolemia and Familial Mediterranean Fever Identified by Whole Exome Sequencing

作者：Tada Hayato; Kawashiri Masa aki; Okada Hirofumi; Endo Saori; Toyoshima Yuka; Konno Tetsuo; Nohara Atsushi; Inazu Akihiro; Takao Akira; Mabuchi Hiroshi; Yamagishi Masakazu; Hayashi Kenshi

来源：Journal of Atherosclerosis and Thrombosis, 2016, 23(7): 884-890.

DOI：10.5551/jat.34827

• Sitosterolemia
• Familial Mediterranean fever
• ABCG5
• ABCG8
• 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.

• 出版日期2016
• 单位河北医科大学