Scholarlink

<p>Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein (LDL) levels, leading to early-onset cardiovascular disease. FH is primarily caused by pathogenic variants in the <i>LDLR</i> gene, affecting cholesterol metabolism. We describe a family with a mild form of FH, in which gene panel sequencing identified a novel c.-8C&gt;A variant in the <i>LDLR</i> 5′UTR. To assess its functional impact, we performed a luciferase assay and found that this variant partially reduces <i>LDLR</i> protein translation efficiency by introducing a novel upstream AUG (uAUG) start codon. This partial reduction in <i>LDLR</i> activity is consistent with the mild phenotype observed in the family. Additionally, we analyzed three previously reported <i>LDLR</i> 5′UTR variants (c.-5C&gt;T, c.-14C&gt;A, and c.-23A&gt;C) but did not observe any significant effect on <i>LDLR</i> expression, suggesting that these variants are unlikely to contribute to disease development. These findings highlight the role of 5′UTR variants in <i>LDLR</i> expression and emphasize the importance of functional studies in variant classification for FH diagnostics.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

uAUG-creating variant in the LDLR gene causes mild Familial hypercholesterolemia

  • 期刊论文

  • 发表日期：

    2025年8月25日

查看全文
  • Alexandra Filatova,
  • Petr Vasiluev,
  • Evgeniya Osipova,
  • Olga Ivanova,
  • Natalia Semenova,
  • Mikhail Skoblov

摘要

Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein (LDL) levels, leading to early-onset cardiovascular disease. FH is primarily caused by pathogenic variants in the LDLR gene, affecting cholesterol metabolism. We describe a family with a mild form of FH, in which gene panel sequencing identified a novel c.-8C>A variant in the LDLR 5′UTR. To assess its functional impact, we performed a luciferase assay and found that this variant partially reduces LDLR protein translation efficiency by introducing a novel upstream AUG (uAUG) start codon. This partial reduction in LDLR activity is consistent with the mild phenotype observed in the family. Additionally, we analyzed three previously reported LDLR 5′UTR variants (c.-5C>T, c.-14C>A, and c.-23A>C) but did not observe any significant effect on LDLR expression, suggesting that these variants are unlikely to contribute to disease development. These findings highlight the role of 5′UTR variants in LDLR expression and emphasize the importance of functional studies in variant classification for FH diagnostics.