Bouhouche A, Benomar A, Birouk N, Bouslam N, Ouazzani R, Yahyaoui M, Chkili T
Laboratoire de Neurogénétique, Service de Neurologie, Hôpital des Spécialités, BP 6220, Rabat-Instituts, Morocco.
J Neurol. 2003 Oct;250(10):1209-13. doi: 10.1007/s00415-003-0186-1.
Spinal muscular atrophy (SMA) is an autosomal recessive motor neuropathy characterized by selective degeneration of anterior horn cells of the spinal cord. Childhood SMA is divided into three types (I-III) on the basis of age of onset and severity. These disorders have been linked to the 5q13 region, where mutations in the Survival Motor Neuron 1 (SMN1) gene have been found in affected individuals. In the case of adult-onset SMA (type IV), on the other hand, reports of homozygous absence of SMN1 gene have been rare. We conducted deletion analysis of SMN and a neighboring gene, NAIP (neuronal apoptosis inhibiting protein). Among 54SMA patients (types I-IV), all of Moroccan origin, Exon 7 of the SMN1 gene was homozygously absent in 100% of type I, 90% of type II, 74% of type III and 80% of type IV SMA patients. Deletion of SMN1 exon 8 was detected in 100% of type I, 53% of type II, 53% of type III and 80% of type IV patients. NAIP exon 5 was homozygously deleted in 67% of type I, 32% of type II, 5% of type III and 20% of type IV SMA patients. Thirty control individuals who were studied had normal SMN1 and NAIP genes. Our results show a high incidence of SMN1 gene deletion in adult-onset SMA patients indicating that SMN1 is the autosomal recessive adult SMA-causing gene. While NAIP is commonly deleted in SMA, this is unlikely to affect disease severity; it was deleted in two adult SMA patients with mild phenotypes.
脊髓性肌萎缩症（SMA）是一种常染色体隐性运动神经病，其特征为脊髓前角细胞的选择性退化。儿童SMA根据发病年龄和严重程度分为三种类型（I - III型）。这些疾病与5q13区域有关，在受影响个体中发现生存运动神经元1（SMN1）基因存在突变。另一方面，在成年发病的SMA（IV型）病例中，SMN1基因纯合缺失的报道很少。我们对SMN和一个相邻基因NAIP（神经元凋亡抑制蛋白）进行了缺失分析。在54例SMA患者（I - IV型）中，所有患者均为摩洛哥裔，100%的I型、90%的II型、74%的III型和80%的IV型SMA患者中SMN1基因的外显子7纯合缺失。在100%的I型、53%的II型、53%的III型和80%的IV型患者中检测到SMN1外显子8缺失。67%的I型、32%的II型、5%的III型和20%的IV型SMA患者中NAIP外显子5纯合缺失。研究的30名对照个体的SMN1和NAIP基因正常。我们的结果表明成年发病的SMA患者中SMN1基因缺失的发生率很高，这表明SMN1是导致常染色体隐性成年SMA的基因。虽然NAIP在SMA中通常缺失，但这不太可能影响疾病严重程度；在两名表型较轻的成年SMA患者中发现了NAIP缺失。
