Di Taranto Maria Donata, Giacobbe Carola, Buonaiuto Alessio, Calcaterra Ilenia, Palma Daniela, Maione Giovanna, Iannuzzo Gabriella, Di Minno Matteo Nicola Dario, Rubba Paolo, Fortunato Giuliana
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, 80131 Naples, Italy.
CEINGE S.C.a r.l. Biotecnologie Avanzate, 80131 Naples, Italy.
J Clin Med. 2020 Jan 14;9(1):219. doi: 10.3390/jcm9010219.
Homozygous familial hypercholesterolemia (HoFH), the severest form of familial hypercholesterolemia (FH), is characterized by very high LDL-cholesterol levels and a high frequency of coronary heart disease. The disease is caused by the presence of either a pathogenic variant at homozygous status or of two pathogenic variants at compound heterozygous status in the , , genes. We retrospectively analyzed data of 23 HoFH patients (four children and 19 adults) identified during the genetic screening of 724 FH patients. Genetic screening was performed by sequencing FH causative genes and identifying large rearrangements of . Among the HoFH patients, four out of 23 (17.4%) were true homozygotes, whereas 19 out of 23 (82.6%) were compound heterozygotes for variants in the gene. Basal LDL-cholesterol was 12.9 ± 2.9 mmol/L. LDL-cholesterol levels decreased to 7.2 ± 1.8 mmol/L when treated with statin/ezetimibe and to 5.1 ± 3.1 mmol/L with anti- antibodies. Homozygous patients showed higher basal LDL-cholesterol and a poorer response to therapy compared with compound heterozygotes. Since 19 unrelated patients were identified in the Campania region (6,000,000 inhabitants) in southern Italy, the regional prevalence of HoFH was estimated to be at least 1:320,000. In conclusion, our results revealed a worse phenotype for homozygotes compared with compound heterozygotes, thereby highlighting the role of genetic screening in differentiating one genetic status from the other.
纯合子家族性高胆固醇血症（HoFH）是家族性高胆固醇血症（FH）最严重的形式，其特征是低密度脂蛋白胆固醇水平极高且冠心病发病率高。该疾病是由 、 、 基因中纯合状态的致病变异或复合杂合状态的两个致病变异引起的。我们回顾性分析了在对724例FH患者进行基因筛查期间确定的23例HoFH患者（4名儿童和19名成人）的数据。通过对FH致病基因进行测序并鉴定 的大片段重排来进行基因筛查。在HoFH患者中，23例中有4例（17.4%）为真正的纯合子，而23例中有19例（82.6%）为 基因变异的复合杂合子。基础低密度脂蛋白胆固醇为12.9±2.9 mmol/L。使用他汀类药物/依折麦布治疗时，低密度脂蛋白胆固醇水平降至7.2±1.8 mmol/L，使用抗 抗体治疗时降至5.1±3.1 mmol/L。与复合杂合子相比，纯合子患者的基础低密度脂蛋白胆固醇更高，对治疗的反应更差。由于在意大利南部坎帕尼亚地区（600万居民）发现了19例无亲缘关系的患者，因此HoFH的地区患病率估计至少为1:320,000。总之，我们的结果显示纯合子的表型比复合杂合子更差，从而突出了基因筛查在区分这两种遗传状态方面的作用。
