Homozygous SMN2 deletion is a protective factor in the Swedish ALS population

Abstract

Abnormal survival motor neuron 1 (SMN1)-copy number has been associated with an increased risk of amyotrophic lateral sclerosis (ALS) in French and Dutch population studies. The aim of this study was to determine whether SMN gene copy number increases the risk of ALS or modulates its phenotype in a cohort of Swedish sporadic ALS (SALS) patients. In all, 502 Swedes with SALS and 502 Swedish controls matched for gender and age were enrolled. SMN1 and SMN2 gene copy numbers were studied by a semiquantitative PCR method. A genotype-phenotype comparison was performed in order to determine whether SMN genes modulate the phenotype of ALS. The results were also compared with our previously reported French cohort of ALS patients. There was no difference between Swedish patients and controls in the frequency of SMN1 and SMN2 copy numbers. The frequency of SMN1 gene copies differed significantly between the French and Swedish ALS populations. The duration of the disease was significantly longer in the Swedish cohort with homozygous deletions of SMN2 when compared with the French cohort. Abnormal SMN1 gene copy number cannot be considered as a universal genetic susceptibility factor for SALS and this result underlines the importance of reproducing association gene studies in groups from different origins. We also suggest that SMN2 gene copy number might have different effects on ALS progression in disparate human populations.

Spinal Muscular Atrophy in the Black South African Population: A Matter of Rearrangement?

“…In this study, 50.8% of N/N b individuals were found to have multiple (3-6) copies of SMN1, exon 7, which is similar to previous reports of 46.8% (Hendrickson et al, 2009) and 47.1% (Sugarman et al, 2012) in African-American individuals and a combined percentage of 48.6% in sub-Saharan African populations (Mali, Nigeria and Kenya) (adapted from Sangaré et al, 2014). In contrast, N/N w individuals have a much lower percentage of multiple SMN1, exon 7 copies of 3.3%, which is comparable to previous reports of 6.3% in white North-American populations (Hendrickson et al, 2009) and a combined percentage of 2.6% in European populations (Germany, France and Sweden) (summarized in Figure 1, Feldkötter et al, 2002;Corcia et al, 2012).…”

Genome-Wide Copy Number Variation in Sporadic Amyotrophic Lateral Sclerosis in the Turkish Population: Deletion of EPHA3 Is a Possible Protective Factor

“…In a recent study, duplication of the SMN1 gene, responsible for spinal muscular atrophy, has been associated with sALS [6]; furthermore, homozygous SMN2 deletions were found to be protective in the Swedish population [7]. In this study, we have investigated for the first time the presence of CNVs in a Turkish ALS cohort with matched healthy controls; we were able to identify several candidates that may impact the development of ALS in the Turkish population.…”

Therapeutic Potential of Mood Stabilizers Lithium and Valproic Acid: Beyond Bipolar Disorder

“…Although the roles of SMN2 were reported to be inconclusive (Veldink et al, 2001;Blauw et al, 2012;Corcia et al, 2012), genetic studies suggest that SMN expression helps to modify disease severity in both SOD1 mouse models (Kunst et al, 2000) and patients with sporadic ALS (Veldink et al, 2001). Lower SMN2 copy numbers and lower SMN protein levels were found to be associated with an increased susceptibility to and severity of ALS Veldink et al, 2005).…”