Passos-Bueno M R, Moreira E S, Vainzof M, Marie S K, Zatz M
Departamento de Biologia, Instituto de Biociências, São Paulo, Brazil.
Hum Mol Genet. 1996 Jun;5(6):815-20. doi: 10.1093/hmg/5.6.815.
Limb-girdle muscular dystrophies (LGMDs) represent a clinically heterogeneous group of genetic diseases characterised by progressive weakness of the pelvic and shoulder girdle muscles. An autosomal dominant form (LGMD1A) has been mapped at 5q22.3-31.3, while five genes responsible for the autosomal recessive forms were mapped respectively at: 15q15.1 (LGMD2A), 2p12-p16 (LGMD2B), 13q12 (LGMD2C), 17q12-q21.33 (LGMD2D) and 4q12 (LGMD2E). Among 17 autosomal recessive (AR) LGMD Brazilian families with at least three affected sibs, we were able to exclude four families (one mild and three severe) from all these five known loci as well as from the dystroglycan and syntrophin genes. Therefore, we have performed a genome-wide search in two of the severely affected families, which are alpha-sarcoglycan negative. We demonstrate linkage of these two Duchenne muscular dystrophy-like families to 5q33-34, and propose to classify them as LGMD2F. In addition, linkage analysis in the other two genealogies that are alpha-sarcoglycan positive suggests that there is at least one other gene which causes AR LGMD.
肢带型肌营养不良症（LGMDs）是一组临床异质性的遗传性疾病，其特征为骨盆带和肩胛带肌肉进行性无力。一种常染色体显性形式（LGMD1A）已被定位于5q22.3 - 31.3，而导致常染色体隐性形式的五个基因分别定位于：15q15.1（LGMD2A）、2p12 - p16（LGMD2B）、13q12（LGMD2C）、17q12 - q21.33（LGMD2D）和4q12（LGMD2E）。在17个常染色体隐性（AR）LGMD巴西家庭中，每个家庭至少有三个患病同胞，我们能够将其中四个家庭（一个轻度和三个重度）排除在所有这五个已知基因座以及肌营养不良聚糖和肌营养不良蛋白聚糖基因之外。因此，我们对其中两个严重受累且α - 肌聚糖阴性的家庭进行了全基因组搜索。我们证明这两个杜兴氏肌营养不良样家庭与5q33 - 34连锁，并提议将它们归类为LGMD2F。此外，对另外两个α - 肌聚糖阳性家系的连锁分析表明，至少还有一个其他基因可导致AR LGMD。
