ABSTRACT Hutchinson-Gilford progeria syndrome (HGPS) is a sporadic, autosomal dominant disorder characterized by premature and accelerated aging symptoms leading to death at the mean age of 14.6 years usually due to cardiovascular complications. HGPS is caused by a de novo point mutation in the LMNA gene encoding the intermediate filament proteins lamins A and C which are structural components of the nuclear lamina. This mutation leads to the production of a truncated toxic form of lamin A, issued from aberrant splicing and called progerin. Progerin accumulates in HGPS cells’ nuclei and is a hallmark of the disease. Small amounts of progerin are also produced during normal aging. HGPS cells and animal preclinical models have provided insights into the molecular and cellular pathways that underlie the disease and have also highlighted possible mechanisms involved in normal aging. This review reports recent medical advances and treatment approaches for patients affected with HGPS.

中文翻译：

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Hutchinson-Gilford早衰综合征的治疗策略概述

摘要 Hutchinson-Gilford 早衰综合征 (HGPS) 是一种散发性常染色体显性遗传疾病，其特征是过早和加速衰老症状，通常由于心血管并发症导致死亡，平均年龄为 14.6 岁。HGPS 是由编码中间丝蛋白纤层蛋白 A 和 C 的 LMNA 基因中的从头点突变引起的，这些蛋白是核纤层的结构成分。这种突变导致产生截断的有毒形式的核纤层蛋白 A，由异常剪接产生，称为早衰蛋白。Progerin 在 HGPS 细胞的细胞核中积累，是该疾病的标志。在正常衰老过程中也会产生少量早老素。HGPS 细胞和动物临床前模型提供了对导致疾病的分子和细胞途径的见解，并强调了正常衰老的可能机制。本综述报告了受 HGPS 影响的患者的最新医学进展和治疗方法。