Noorian Shahab, Razmandeh Rezvan, Jazayeri Roshanak
Department of Pediatric Endocrinology and Metabolism, Emam Ali Hospital, Alborz University of Medical Sciences, Karaj, Iran.
Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
J Diabetes Metab Disord. 2022 Mar 10;21(1):1201-1205. doi: 10.1007/s40200-022-01007-1. eCollection 2022 Jun.
Familial Hypercholesterolemia is an autosomal, dominant genetic disorder associated with premature cardiovascular disease (CVD). Mutations in the LDLR, APOB, and PCSK9 genes cause the FH phenotype, but in 20% of FH patients, mutations in other genes cause FH. In this regard, we investigated the genetic basis of an Autosomal Dominant Hypercholesterolemia (ADH) phenotype in an Iranian family via next-generation exome sequencing with a panel of hyperlipidemia. We report the first case of FH in an Iranian family due to a mutation in the APOE gene. A 10-year-old female was referred to our genetic clinic with a family history of hypercholesterolemia and high cholesterol level at the age of 3. Evaluation of the lipid profile showed the off total cholesterol of 338 mg/dl, low-density lipoprotein cholesterol (LDL-C of 247 mg/dl(. We identified a mutation in the APOE gene, c.500_502del /p. Leu167del confirmed co-segregation in three individuals of the family from three generations. This in-frame mutation identified here, the first report in Iran, confirms previous reports that ADH can be caused by mutations within the APOE gene and strongly introduces it as the 4th gene that must be checked in the genetic investigating of FH.
家族性高胆固醇血症是一种常染色体显性遗传疾病，与早发性心血管疾病（CVD）相关。低密度脂蛋白受体（LDLR）、载脂蛋白B（APOB）和前蛋白转化酶枯草溶菌素9（PCSK9）基因的突变会导致家族性高胆固醇血症（FH）表型，但在20%的FH患者中，其他基因的突变会导致FH。在这方面，我们通过对一组高脂血症患者进行下一代外显子组测序，研究了一个伊朗家庭中常染色体显性高胆固醇血症（ADH）表型的遗传基础。我们报告了伊朗一个家庭中首例因载脂蛋白E（APOE）基因突变导致的FH病例。一名10岁女性因有高胆固醇血症家族史且3岁时胆固醇水平高而被转诊至我们的遗传诊所。血脂谱评估显示总胆固醇为338毫克/分升，低密度脂蛋白胆固醇（LDL-C）为247毫克/分升。我们在APOE基因中发现了一个突变，即c.500_502del /p.Leu167del，证实该突变在这个家族三代中的三个个体中共同分离。此处发现的这种框内突变是伊朗的首例报告，证实了之前关于ADH可由APOE基因内突变引起的报告，并强烈表明它是FH基因研究中必须检测的第4个基因。
