National Laboratory Astana, Nazarbayev University, Astana 010000, Kazakhstan.
Eurasian Society of Personalized Medicine, Astana 010000, Kazakhstan.
Int J Mol Sci. 2024 Nov 5;25(22):11882. doi: 10.3390/ijms252211882.
Familial hypercholesterolemia is an autosomal hereditary disease defined by an increased level of low-density lipoprotein cholesterol (LDL-C), which predisposes significant risks for premature cardiovascular disorders. We present a family trio study: proband, a 13-year-old Kazakh girl with homozygous familial hypercholesterolemia (HoFH) and her parents. HoFH is much more rare and severe than a heterozygous form of the disorder. HoFH patients generally present with LDL-C levels exceeding 13 mmol/L, resulting in early and life-threatening cardiovascular events within the first decades of life. In cases of neglected treatment, young patients have a risk of death from coronary diseases before the age of 30. The aim of this research was to identify genetic mutations in the affected patient and her parents. Genetic testing was necessary due to highly elevated LDL-C levels and the presence of multiple xanthomas. Targeted next-generation sequencing (NGS) was performed in this study using the Illumina TruSight cardio panel, which targets 174 genes related to cardiac disorders. The girl was diagnosed with HoFH based on the results of genetic testing. A biallelic mutation was observed in exon 3 of the low-density lipoprotein receptor (): c. 295 G>A (p.Glu99Lys). Sanger sequencing confirmed that the mutant gene was inherited from both parents. After confirming the genetic diagnosis of HoFH, the patient was treated with LDL apheresis and statins. This case report is the first study of HoFH in a pediatric patient from the Central Asian region. Globally, it emphasizes the need for increased clinical awareness among healthcare providers, as early detection and intervention are important for improving outcomes, particularly in pediatric patients with this rare genetic disorder.
家族性高胆固醇血症是一种常染色体遗传性疾病，其特征是低密度脂蛋白胆固醇（LDL-C）水平升高，使患者面临发生心血管疾病的高风险，包括过早发病。我们进行了一个家族三代研究，包括先证者，一名 13 岁哈萨克族的纯合子家族性高胆固醇血症（HoFH）女孩，以及她的父母。HoFH 比杂合子形式更为罕见和严重。HoFH 患者的 LDL-C 水平通常超过 13mmol/L，导致患者在生命的头几十年内发生早发且危及生命的心血管事件。如果治疗被忽视，年轻患者有在 30 岁前死于冠心病的风险。本研究的目的是确定受影响患者及其父母的基因突变。由于极高的 LDL-C 水平和多发性黄色瘤的存在，需要进行基因检测。本研究采用靶向 174 个与心脏疾病相关基因的 Illumina TruSight cardio 试剂盒进行了靶向下一代测序（NGS）。该女孩被诊断为 HoFH，基于基因检测结果。在低密度脂蛋白受体（）的exon 3 中观察到双等位基因突变：c.295G>A（p.Glu99Lys）。Sanger 测序证实该突变基因是从父母双方遗传而来。在确认 HoFH 的遗传诊断后，患者接受 LDL 血浆置换和他汀类药物治疗。本病例报告是首例来自中亚地区的儿科患者的 HoFH 研究。在全球范围内，它强调了提高医疗保健提供者的临床意识的必要性，因为早期发现和干预对于改善结果非常重要，尤其是对于患有这种罕见遗传疾病的儿科患者。
