The Hammersmith functional score correlates with the SMN2 copy number: A multicentric study F.D. Tiziano a , E. Bertini b , S. Messina c,d , C. Angelozzi a , M. Pane c , A. D’Amico b , P. Alfieri c , S. Fiori a , R. Battini e , A. Berardinelli f , P. Boffi g , C. Bruno h , C. Cini e , C. Minetti h , T. Mongini i , L. Morandi j , S. Orcesi f , M. Pelliccioni k , A. Pini l , M. Villanova m , G. Vita d , M. Locatelli n , E. Mercuri c,o, * , C. Brahe a a Institute of Medical Genetics, Catholic University, Rome, Italy b Department of Laboratory Medicine, Unit of Molecular Medicine, Bambino Gesu ` Hospital, Rome, Italy c Department of Paediatric Neurology, Catholic University, Rome, Italy d Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, Italy e Department of Developmental Neuroscience, IRCCS Stella Maris, Pisa, Italy f Department of Child Neurology and Psychiatry, IRCCS ‘‘C. Mondino’’ Foundation, University of Pavia, Italy g Department of Child Neuropsychiatry, University of Turin, Italy h Neuromuscular Disease Unit, G. Gaslini Institute, Genoa, Italy i Neuromuscular Center, S.G. Battista Hospital, University of Turin, Italy j Myopathology and Immunolgy Unit, National Neurological Institute C. Besta, Milan, Italy k UILDM, Rome, Italy l Child Neurology and Psychiatry Unit, Maggiore Hospital, Bologna, Italy m Nigrisoli Hospital, Bologna, Italy n Unit of Molecular Medicine and Scientific Directorate, Bambino Gesu ` Hospital, Rome, Italy o Dubowitz Neuromuscular Centre, Hammersmith Hospital, Imperial College, London, UK Received 15 November 2006; received in revised form 6 February 2007; accepted 11 February 2007 Abstract Previous studies showed that SMN2 copy number correlates inversely with the disease severity. Our aim was to evaluate SMN2 copy numbers and the Hammersmith functional motor scale in 87 patients with SMA II in order to establish whether, within SMAII, the number of copies correlates with the severity of functional impairment. Our results showed a relative variability of functional scores, but a significant correlation between the number of SMN2 genes and the level of function. Ó 2007 Published by Elsevier B.V. Keywords: Spinal muscular atrophy; SMA; SMN1; SMN2; Hammersmith functional motor scale 1. Introduction Spinal muscular atrophy (SMA) is clinically subdivided into three types based on age of onset and clinical severity [1,2]. Most SMA patients have homozygous absence of a functional SMN1 gene and it has been demonstrated that the disease clinical sever- ity can be related to the SMN2 copy number [3–6]. Over 80% of patients with type I SMA were found to carry one or two SMN2 copies, whereas 80% of patients with type II had three SMN2 copies, and 96% of patients with type III SMA had three or four 0960-8966/$ - see front matter Ó 2007 Published by Elsevier B.V. doi:10.1016/j.nmd.2007.02.006 * Corresponding author. Address: Department of Paediatric Neu- rology, Catholic University, Largo Gemelli, 00168 Rome, Italy. E-mail address: e.mercuri@imperial.ac.uk (E. Mercuri). www.elsevier.com/locate/nmd Neuromuscular Disorders 17 (2007) 400–403