Louhichi N, Richard P, Triki C H, Meziou M, Ayadi H, Guicheney P, Fakhfakh F
Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, 3029 Sfax, Tunisie.
Arch Inst Pasteur Tunis. 2006;83(1-4):19-23.
Congenital muscular dystrophies are a group of common genetically determined disorders often transmitted with a recessive mode of inheritance. In recent years, several deficiencies of proteins from the muscle membrane, extra cellular matrix, sarcomere, muscle cytosol and the nucleus have been described to cause CMD. The occidental type of CMD (MDC1A) in which the primary defect is a deficiency in laminin alpha2 chain (merosin) encoded by LAMA2 gene, accounts for 30-40% of cases. The clinical course of CMD with complete laminin alpha2 chain deficiency may be variable but most often; severe forms characterized by hypotonia at birth, profound muscle weakness, marked delay in motor milestones are observed. Since the identification of the first LAMA2 gene mutations leading to merosin deficiency in 1995, several mutations have subsequently been reported in many exons of this gene without any "hotspot" region. In this work, we report two novel homozygous mutations c.8005delT and c.8244+1G>A in the LAMA2 gene in four Tunisian patients with a severe MDC1A phenotype belonging to two unrelated consanguineous families.
先天性肌营养不良是一组常见的遗传性疾病，通常以隐性遗传方式传递。近年来，已发现肌肉膜、细胞外基质、肌节、肌肉细胞质和细胞核中的几种蛋白质缺陷可导致先天性肌营养不良。西方型先天性肌营养不良（MDC1A），其主要缺陷是由LAMA2基因编码的层粘连蛋白α2链（巢蛋白）缺乏，占病例的30-40%。完全缺乏层粘连蛋白α2链的先天性肌营养不良的临床病程可能各不相同，但最常见的是观察到严重形式，其特征为出生时肌张力低下、严重肌肉无力、运动发育里程碑明显延迟。自1995年首次鉴定出导致巢蛋白缺乏的LAMA2基因突变以来，随后在该基因的许多外显子中报道了多个突变，且无任何“热点”区域。在本研究中，我们报告了4名患有严重MDC1A表型的突尼斯患者中LAMA2基因的两个新的纯合突变c.8005delT和c.8244+1G>A，这4名患者来自两个无亲缘关系的近亲家庭。
