Cardiovascular Prevention Unit, Adult Cardiology Department, Prince Sultan Cardiac Centre, Riyadh, SA.
Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, Makkah Al Mukarramah, SA.
Glob Heart. 2020 Feb 28;15(1):19. doi: 10.5334/gh.759.
Familial hypercholesterolemia (FH) is an autosomal dominant inherited genetic disorder and results in the development of coronary artery disease (CAD). Clinical diagnosis of homozygous HH patients is usually straightforward because persistent hypercholesterolemia can produce xanthoma and corneal arcus. However, xanthoma may also be misdiagnosed as skin lesions and could therefore be mistreated. The aim of this case study report is to highlight the plight of patients with FH as means of raising awareness of the condition among dermatologists and health care practitioners, also to determine the genotype-phenotype correlation in severely affected homozygous FH proband patients.
Genetic screening of FH associated genes was performed by Ion Torrent next-generation sequencing and cascade screening by capillary sequencing.
We present two clinical cases with prominent skin lesions seen in a dermatology clinic that were referred to plastic surgery for excision. Genetic testing was performed later, and confirmed common single nucleotide deletion variant (c.2027delG) in the alleles consequent to a frameshift mutation p.(G676Afs33). In addition to the variant, two possibly damaging variants p.(L3313I) and p.(L1212M) and three damaging variants p.(R19), p.(G83Q) and p.(S474*) in and genes respectively were identified. The gene variant p.(G83Q) was found to be novel, while others have been previously reported. Both patients were refractory to pharmacological therapies and are currently on lipoprotein apheresis (LA).
The present report indicates the need for increased awareness of FH, among the public and healthcare practitioners and supports the need for diagnostic screening and cascade genetic testing of this high-risk condition, which could ultimately lead to better prevention of CHD in this lethal condition.
家族性高胆固醇血症（FH）是一种常染色体显性遗传的基因疾病，可导致冠状动脉疾病（CAD）的发生。杂合 HH 患者的临床诊断通常很简单，因为持续性高胆固醇血症会导致黄斑瘤和角膜弓的形成。然而，黄斑瘤也可能被误诊为皮肤病变，因此可能会被误诊和误治。本病例研究报告的目的是强调 FH 患者的困境，以提高皮肤科医生和医疗保健从业者对该病的认识，并确定严重受影响的纯合 FH 先证者患者的基因型-表型相关性。
通过 Ion Torrent 下一代测序和毛细管测序进行 FH 相关基因的遗传筛查。
我们介绍了两个在皮肤科诊所就诊时出现明显皮肤病变的临床病例，这些病变被转诊到整形外科进行切除。随后进行了基因检测，证实了 等位基因中常见的单核苷酸缺失变异（c.2027delG），导致移码突变 p.（G676Afs33）。除了 变异外，还鉴定了 基因中的两个可能具有破坏性的 变异 p.（L3313I）和 p.（L1212M）以及 基因中的三个破坏性变异 p.（R19）、p.（G83Q）和 p.（S474*）。 基因中的变异 p.（G83Q）是新发现的，而其他变异先前已有报道。这两个患者对药物治疗均无反应，目前正在接受脂蛋白吸附（LA）治疗。
本报告表明，需要提高公众和医疗保健从业者对 FH 的认识，并支持对这种高风险疾病进行诊断性筛查和级联遗传检测，这最终可能会改善这种致命疾病的 CHD 预防。
