Rivas E, Teijeira S, dos Santos M R, Porrit I, Leturcq F, Fernandez J M, Navarro C
Pathology and Neuropathology Service, Meixoeiro Hospital, Vigo, Spain.
Acta Myol. 2004 Dec;23(3):159-62.
Out of 10 autosomal recessive limb-girdle muscular dystrophies reported, 4 are caused by mutations in the genes encoding for sarcoglycans (alpha-, beta-, gamma- and delta-SG). Beta-sarcoglycanopathy (limb-girdle muscular dystrophy 2E) is a genetically heterogeneous disorder which usually presents a severe progressive clinical course. A complete immunohistochemical evaluation of the sarcoglycan complex should be carried out to direct the mutation analysis approach. The present report concerns a Spanish family with a genetically confirmed beta-sarcoglycanopathy. The patient, a 16-year-old female, offspring of a consanguineous marriage, developed a severe limb-girdle muscular dystrophy with a Duchenne-like phenotype. Muscle biopsy showed dystrophic changes and complete absence of the four sarcoglycans. Genetic analysis demonstrated homozygosis for the M100K missense mutation in exon 3, encoding for the proximal extracellular domain. The parents and one sister were found to be carriers. Missense mutations affecting this domain result in the instability of the entire sarcoglycan complex and lead to severe phenotypes as seen in non-sense mutations.
在已报道的10种常染色体隐性肢带型肌营养不良症中，有4种是由编码肌聚糖（α -、β -、γ -和δ - SG）的基因突变引起的。β - 肌聚糖病（肢带型肌营养不良症2E）是一种遗传异质性疾病，通常呈现严重的进行性临床病程。应进行肌聚糖复合物的完整免疫组织化学评估，以指导突变分析方法。本报告涉及一个经基因确诊为β - 肌聚糖病的西班牙家庭。该患者为一名16岁女性，是近亲结婚的后代，患有一种具有杜氏样表型的严重肢带型肌营养不良症。肌肉活检显示营养不良性改变且四种肌聚糖完全缺失。基因分析表明，外显子3中编码近端细胞外结构域的M100K错义突变呈纯合状态。发现其父母和一个姐姐为携带者。影响该结构域的错义突变会导致整个肌聚糖复合物不稳定，并导致如无义突变所见的严重表型。
