Driss A, Amouri R, Ben Hamida C, Souilem S, Gouider-Khouja N, Ben Hamida M, Hentati F
National Institute of Neurology, La Rabta, 1007, Tunis, Tunisia.
Neuromuscul Disord. 2000 Jun;10(4-5):240-6. doi: 10.1016/s0960-8966(00)00099-7.
Autosomal recessive limb-girdle muscular dystrophies represent a genetically heterogeneous group of diseases characterized by a progressive involvement of skeletal muscles. They show a wide spectrum of clinical courses, varying from very mild to severe. Eight loci responsible for autosomal recessive limb-girdle muscular dystrophies have been mapped and six defective genes identified. In this study, we report the clinical data, muscle biopsy findings and results of genetic linkage analysis in a large consanguineous Tunisian family with 13 individuals suffering from autosomal recessive limb-girdle muscular dystrophy. Clinical features include variable age of onset, proximal limb muscle weakness and wasting predominantly affecting the pelvic girdle, and variable course between siblings. CK rate was usually high in younger patients. Muscle biopsy showed dystrophic changes with normal expression of dystrophin and various proteins of the dystrophin-associated protein complex (sarcoglycan sub-units, dystroglycan, and sarcospan). Genetic linkage analysis excluded the known limb-girdle muscular dystrophies loci as well as ten additional candidate genes. A maximum LOD score of 4.36 at θ=0.00 was obtained with marker D19S606, mapping this new form of autosomal recessive limb-girdle muscular dystrophy to chromosome 19q13.3.
常染色体隐性遗传性肢带型肌营养不良症是一组具有遗传异质性的疾病，其特征为骨骼肌进行性受累。它们呈现出广泛的临床病程，从非常轻微到严重不等。已经定位了8个与常染色体隐性遗传性肢带型肌营养不良症相关的基因座，并鉴定出6个缺陷基因。在本研究中，我们报告了一个来自突尼斯的近亲家庭的临床数据、肌肉活检结果以及遗传连锁分析结果，该家庭中有13名个体患有常染色体隐性遗传性肢带型肌营养不良症。临床特征包括发病年龄不一、近端肢体肌肉无力和萎缩，主要影响骨盆带，且兄弟姐妹之间病程各异。年轻患者的肌酸激酶（CK）水平通常较高。肌肉活检显示营养不良性改变，肌营养不良蛋白以及肌营养不良蛋白相关蛋白复合物的各种蛋白质（肌聚糖亚基、肌营养不良聚糖和肌膜蛋白）表达正常。遗传连锁分析排除了已知的肢带型肌营养不良症基因座以及另外10个候选基因。在θ=0.00时，标记D19S606获得了最大对数优势分数（LOD）4.36，将这种新形式的常染色体隐性遗传性肢带型肌营养不良症定位于19号染色体q13.3区域。
