A Rare Coincidence of Sitosterolemia and Familial Mediterranean Fever Identified by Whole Exome Sequencing
A Rare Coincidence of Sitosterolemia and Familial Mediterranean Fever Identified by Whole Exome Sequencing
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DOI：
10.5551/jat.34827
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发表时间：
2016-01-01
影响因子：
4.4
通讯作者：
Hayashi, Kenshi
中科院分区：
文献类型：
--
作者：
Tada, Hayato;Kawashiri, Masa-aki;Hayashi, Kenshi
全外显子组测序（WES）技术加速了孟德尔遗传病的遗传学研究，诊断成功率约为30%。我们遇到了一个13岁的日本女性，最初诊断为家族性高胆固醇血症的基础上，严重的高胆固醇血症（初始LDL胆固醇= 609毫克/分升，在1岁）和全身性intertriginous黄瘤的历史，发烧和关节炎的复发性自限性发作的临床表现。她的两种表型似乎以隐性方式共分离。我们对这个病人进行了WES，他被认为是先证者。在该个体中发现的206，430种变异中，我们发现了18，220种无义，错义或剪接位点变异，其中3，087种是罕见的（次要等位基因频率A或p.Arg419His/c。1763-1G> A [剪接受体位点]）和MEFV基因中的双复合杂合突变（c.329T>C/C或p.Leu110Pro/c.442G>C/C或p.Glu148Val）。该患者首次使用WES基因诊断为谷甾醇血症和家族性地中海热。这样一个全面的方法是有用的，以确定多种不相关的遗传性疾病的致病突变。
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 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.