SMN1 gene duplications are more frequent in patients with progressive muscular atrophy

Abstract

Survival Motor Neuron 1 (SMN1) is a causative gene for autosomal recessive infantile and juvenile proximal spinal muscular atrophy. SMN1 duplications have recently been found to increase susceptibility to amyotrophic lateral sclerosis. The role of centromeric SMN copy (SMN2) has been postulated in progressive muscular atrophy (PMA). The aim of this study was to analyse the SMN1 and SMN2 copy number variations in patients with PMA. SMN1 and SMN2 genotype was studied in 87 patients with PMA, diagnosed at the Department of Neurology, Medical University of Warsaw, between 1992 and 2012 and in 600 healthy controls. Results demonstrated that three copies of SMN1 were found in 8.1% of PMA patients and in 24% of PMA patients with disease duration above 48 months compared to 4.6% of the general population. Patients with three SMN1 copies had a limb onset, lower median age of onset and longer disease duration compared to patients with two SMN1 copies. There were no significant differences in the SMN2 copy numbers. In conclusion, the increased copy number of SMN1 may be a susceptibility factor to PMA and influence the clinical phenotype.

Key words::

• Progressive muscular atrophy
• survival of motor neuron
• SMN1
• SMN2

Acknowledgements

This study was supported by the grant N N402 373539 (MK-K) and N N401 011038 (MJ) from the Ministry of Science and Higher Education of Poland. The authors wish to thank Dr. Mitsuya Morita, for SOD1, ANG and TARDBP screening of 16 PMA patients; Ms Anna Królikowska, for excellent technical support; and Prof. Anna Barańczyk-Kuźma, for critical reading of the manuscript.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.