Sphitzen Shoshi, Golomb Mordechai, Mowaswes Mohammad, Bitzur Refael, Horowitz Cederboim Smadar, Leker Ronen R, Gotkine Marc, Chovers Itai, Schurr Daniel, Leitersdorf Eran, Durst Ronen
Lipid Clinic and Center for Cardiovascular Precision Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Cardiology Department, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Front Cardiovasc Med. 2025 May 22;12:1553259. doi: 10.3389/fcvm.2025.1553259. eCollection 2025.
High-Density Lipoprotein Cholesterol (HDL-C) plays a pivotal role in cardiovascular health, acting as a key component in lipid transport and atheroprotection. While low HDL-C levels in the general population are often the result of multifactorial causes, extremely low HDL-C levels (<20 mg/dl) are rare and may be attributed to underlying genetic defects. Mutations in genes such as , , and -although exceedingly rare-have been linked to profound alterations in lipid metabolism, often resulting in significant morbidity and increased cardiovascular risk.
In this study, we used exome sequencing on patients with very low HDL-C.
We identified three patients with pathogenic mutations associated with genetic low HDL-C syndrome, including [NM_005502.4(ABCA1):c.4175 + 1G > T, chr:9 91757308° C > A, rs375247413], LCAT [NM_000229.2(LCAT):c.349G > A p.Ala117Thr, rs28940886], and [NM_000039.3(APOA1):c.388A > T, p.Lys130*].
Each case presented a unique spectrum of clinical phenotypes, systemic complications, and biochemical abnormalities, illustrating the diverse impact of these genetic mutations. We provide a detailed analysis of the clinical and biochemical profiles of these patients, highlighting key aspects of disease manifestation and progression. This report underscores the importance of recognizing and characterizing rare genetic causes of low HDL-C, which may have profound implications for patient care and risk stratification.
高密度脂蛋白胆固醇（HDL-C）在心血管健康中起着关键作用，是脂质转运和抗动脉粥样硬化保护的关键组成部分。虽然普通人群中HDL-C水平低通常是多因素导致的，但极低的HDL-C水平（<20mg/dl）很少见，可能归因于潜在的基因缺陷。诸如 、 和 等基因的突变——尽管极其罕见——已与脂质代谢的深刻改变相关联，常常导致显著的发病率和心血管风险增加。
在本研究中，我们对HDL-C水平极低的患者进行了外显子组测序。
我们鉴定出三名患有与遗传性低HDL-C综合征相关的致病突变的患者，包括 [NM_005502.4(ABCA1):c.4175+1G>T，chr:9 91757308°C>A，rs375247413]、卵磷脂胆固醇酰基转移酶（LCAT）[NM_000229.2(LCAT):c.349G>A p.Ala117Thr，rs28940886]和 [NM_000039.3(APOA1):c.388A>T，p.Lys130*]。
每个病例都呈现出独特的临床表型、全身并发症和生化异常谱，说明了这些基因突变的不同影响。我们对这些患者的临床和生化特征进行了详细分析，突出了疾病表现和进展的关键方面。本报告强调了识别和表征低HDL-C的罕见遗传原因的重要性，这可能对患者护理和风险分层具有深远意义。
