面肩肱型肌营养不良症的分子遗传学研究进展

面肩肱型肌营养不良症（factoscapulohumeral muscular dystrophy,FSHD)呈常染色体显性遗传。大多数致病基因定位于4q35，存在遗传异质性。发现与FSHD相关的DNA重组，即4q35上3．3kb串联重复单位呈不同拷贝数缺失。以p13E-11为探针检测EcoR I/Bln I双重消化的DNA片段，FSHD患者的消化片段通常小于正常人，从而进行有效的分子诊断。由于FSHD基因尚未鉴定与分子，FSHD的确切发病机理仍未阐明，提出有位置效应变异假说等。目前有一候选基因FRG1。与FSHD相关的DNA重组片段的大小与FSHD临床表型之间显著相关，可较好地解释FSHD患者广泛的临床变异性。

Progress in researches on the molecular genetics of facioscapulohumeral muscular dystrophy

Facioscapulohumeral muscular dystrophy(FSHD) is an autosomal dominant neuromuscular disorder characterized by progressive weakness of the facial, shoulder and upper arm muscles. The major gene involved has been mapped to chromosome 4q35. There is the evidence for genetic heterogeneity. The FSHD- associated DNA rearrangements are due to deletions of integral copies of the 3.3 kb tandem repeated unit from the subtelomeric region on chromosome 4q35. A valuable molecular diagnostic test for FSHD has been created with the use of p13E-11 probe to detect the EcoR I/Bln I double digestion fragment which is usually smaller in FSHD patient than in normal indivdual. Since the FSHD gene has not been identified yet, the exact molecular pathogenesis of FSHD remains unclear. The hypothesis of position effect variegation has been postulated as the underlying genetic mechanism of FSHD. FRG1 (FSHD region gene 1) from human chromosome 4q35 is identified as a candidate gene for FSHD. A significant correlation between the size of rearrangements associated with FSHD and the clinical phenotype has been found. The various rearrangement fragment size may explain the wide range of clinical severity in FSHD.