摘要：

面-肩-肱型肌营养不良症（FSHD）呈常染色体显性遗传，以面肌、肩胛带肌和上臂肌群肌无力和肌萎缩发病，逐渐累及躯干肌群和下肢肌群，临床异质性较高，预后相对较好。临床分型包括FSHD1 型和FSHD2 型，前者与4q35 区域D4Z4 串联重复序列缺失有关，其上游简单序列长度多态性和下游特殊等位序列4qA/4qB 具有选择致病性。4q35 区域DNA 低甲基化启动表观遗传效应，使D4Z4 串联重复序列内DUX4 基因去抑制致异常表达，导致多种肌细胞损害效应。后者由DNA 甲基化调控基因——SMCHD1 基因突变所致。支持面-肩-肱型肌营养不良症是毒性功能获得性疾病学说，为其治疗研究提供重要靶点。

关键词: 营养不良, 面肩肱型, 基因, 突变, 综述

Abstract:

Facioscapulohumeral muscular dystrophy (FSHD), characterized by symmetric or asymmetric muscular weakness of the initial onset of facial, shoulder-girdle and upper arm muscles, and descending to limb muscles, is a classical autosomal dominant myopathy with high clinical diversity and relatively good prognosis. FSHD is catigorized into two types, FSHD1 and FSDH2. Previous studies have demonstrated that 95% patients with FSHD1 were associated with a contraction of D4Z4 microsatellite repeats on chromosome 4q35, which was pathogenic in the genetic backgrounds, including a special sequence of simple sequence length polymorphism (SSLP) proximal to the D4Z4 repeats and the 4qA/4qB polymorphism distal to the repeats. In recent years, several reports have confirmed that 4q35 locus leads to DNA hypomethylation and inner DUX4 gene transcription by epigenetic effect. The abnormal expression of DUX4 further activates several genes, which inhibit myogenesis, sensitize cells to oxidative stress and induce muscle atrophy. And not only that, FSHD2 is formed by another methylation regulation gene—— SMCHD1 mutations. More and more evidences supported that toxic gain of function mechanism plays an important role in the occurrence of FSHD. The DUX4 gene becomes an important target for treatment study in the future.

Key words: Muscular dystrophy, facioscapulohumeral, Genes, Mutation, Review