Richard I, Broux O, Allamand V, Fougerousse F, Chiannilkulchai N, Bourg N, Brenguier L, Devaud C, Pasturaud P, Roudaut C
Généthon, Evry, France.
Cell. 1995 Apr 7;81(1):27-40. doi: 10.1016/0092-8674(95)90368-2.
Limb-girdle muscular dystrophies (LGMDs) are a group of inherited diseases whose genetic etiology has yet to be elucidated. The autosomal recessive forms (LGMD2) constitute a genetically heterogeneous group with LGMD2A mapping to chromosome 15q15.1-q21.1. The gene encoding the muscle-specific calcium-activated neutral protease 3 (CANP3) large subunit is located in this region. This cysteine protease belongs to the family of intracellular calpains. Fifteen nonsense, splice site, frameshift, or missense calpain mutations cosegregate with the disease in LGMD2A families, six of which were found within La Réunion island patients. A digenic inheritance model is proposed to account for the unexpected presence of multiple independent mutations in this small inbred population. Finally, these results demonstrate an enzymatic rather than a structural protein defect causing a muscular dystrophy, a defect that may have regulatory consequences, perhaps in signal transduction.
肢带型肌营养不良症（LGMDs）是一组遗传病因尚未阐明的遗传性疾病。常染色体隐性遗传形式（LGMD2）构成了一个基因异质性群体，其中LGMD2A定位于染色体15q15.1 - q21.1。编码肌肉特异性钙激活中性蛋白酶3（CANP3）大亚基的基因位于该区域。这种半胱氨酸蛋白酶属于细胞内钙蛋白酶家族。在LGMD2A家族中，有15个无义、剪接位点、移码或错义钙蛋白酶突变与该疾病共分离，其中6个是在留尼汪岛患者中发现的。有人提出了双基因遗传模型来解释这个小近亲群体中多个独立突变的意外出现。最后，这些结果表明，一种酶缺陷而非结构蛋白缺陷导致了肌营养不良症，这种缺陷可能具有调节作用，或许在信号转导方面。
