Sifi Y, Sifi K, Boulefkhad A, Abadi N, Bouderda Z, Cheriet R, Magen M, Bonnefont J P, Munnich A, Benlatreche C, Hamri A
Service of Neurology CHU of Constantine, Algeria ; Laboratory of Biology and Molecular Genetics CHU and University of Constantine, Algeria.
Laboratory of Biology and Molecular Genetics CHU and University of Constantine, Algeria ; Laboratory of Biochemistry CHU of Constantine, Algeria.
J Neurodegener Dis. 2013;2013:903875. doi: 10.1155/2013/903875. Epub 2013 Mar 24.
Spinal muscular atrophy (SMA) is the second most common lethal autosomal recessive disorder. It is divided into the acute Werdnig-Hoffmann disease (type I), the intermediate form (type II), the Kugelberg-Welander disease (type III), and the adult form (type IV). The gene involved in all four forms of SMA, the so-called survival motor neuron (SMN) gene, is duplicated, with a telomeric (tel SMN or SMN1) and a centromeric copy (cent SMN or SMN2). SMN1 is homozygously deleted in over 95% of SMA patients. Another candidate gene in SMA is the neuronal apoptosis inhibitory protein (NAIP) gene; it shows homozygous deletions in 45-67% of type I and 20-42% of type II/type III patients. Here we studied the SMN and NAIP genes in 92 Algerian SMA patients (20 type I, 16 type II, 53 type III, and 3 type IV) from 57 unrelated families, using a semiquantitative PCR approach. Homozygous deletions of SMN1 exons 7 and/or 8 were found in 75% of the families. Deletions of exon 4 and/or 5 of the NAIP gene were found in around 25%. Conversely, the quantitative analysis of SMN2 copies showed a significant correlation between SMN2 copy number and the type of SMA.
脊髓性肌萎缩症(SMA)是第二常见的致死性常染色体隐性疾病。它分为急性韦尔尼克 - 霍夫曼病(I型)、中间型(II型)、库格尔贝格 - 韦兰德病(III型)和成人型(IV型)。涉及所有四种SMA类型的基因,即所谓的生存运动神经元(SMN)基因,是重复的,有一个端粒拷贝(端粒SMN或SMN1)和一个着丝粒拷贝(着丝粒SMN或SMN2)。超过95%的SMA患者中SMN1是纯合缺失的。SMA中的另一个候选基因是神经元凋亡抑制蛋白(NAIP)基因;在45 - 67%的I型患者和20 - 42%的II/III型患者中它显示为纯合缺失。在此,我们使用半定量PCR方法研究了来自57个无亲缘关系家庭的92例阿尔及利亚SMA患者(20例I型、16例II型、53例III型和3例IV型)的SMN和NAIP基因。在75%的家庭中发现了SMN1外显子7和/或8的纯合缺失。在约25%的患者中发现了NAIP基因外显子4和/或5的缺失。相反,对SMN2拷贝的定量分析显示SMN2拷贝数与SMA类型之间存在显著相关性。