%0 Journal Article
%T Clinical and Genetic Study of Algerian Patients with Spinal Muscular Atrophy
%A Y. Sifi
%A K. Sifi
%A A. Boulefkhad
%A N. Abadi
%A Z. Bouderda
%A R. Cheriet
%A M. Magen
%A J. P. Bonnefont
%A A. Munnich
%A C. Benlatreche
%A A. Hamri
%J Journal of Neurodegenerative Diseases
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/903875
%X 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¨C67% of type I and 20¨C42% 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. 1. Introduction Spinal muscular atrophies (SMAs) are a group of motor neuron disorders characterized by degeneration of spinal cord anterior horn cells, leading to muscular wasting and atrophy [1]. SMA is the most common autosomal recessive disorder after cystic fibrosis, with an estimated 1/10,000 incidence and a 1/60 carrier frequency [2]. Affected patients are classified into four groups according to age at onset and phenotype severity [3, 4]. Type I SMA or the Werdnig-Hoffmann disease (OMIM No. 253300) is the most severe form, with an onset within the first 6 months of age, severe generalized muscle weakness with hypotonia, and death before two years of age. In type II SMA (OMIM No. 253550), affected children sit unassisted, may be able to walk for a short distance, and usually survive over 10 years of age. Type III SMA or the Kugelberg-Welander disease (OMIM No. 253400) has its onset in the first to third decade. Though its course is highly variable, patients are constantly able to walk unassisted. Type IV SMA or adult-onset SMA (OMIM No. 271150) is quite rare. The survival motor neuron (SMN) gene, implicated in the four forms of SMA, maps to chromosome 5q 11.2¨C13.3 [5¨C7] and is duplicated as telomeric and centromeric copies, so called SMN1 (OMIM No. 600354) and SMN2 (OMIM No. 601627), respectively [8, 9]. SMN1 and SMN2 comprising 8 exons are highly homologous, with only five base-pair differences within their 3¡ä
%U http://www.hindawi.com/journals/jnd/2013/903875/