1. Clinical and molecular cross-sectional study of a cohort of adult type III spinal muscular atrophy patients: clues from a biomarker study
- Author
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Cristina Montomoli, Corrado Angelini, Luisa Politano, Tiziana Mongini, Emanuela Abiusi, Maria Barbara Pasanisi, Carla Angelozzi, Alessandra Gaiani, Grazia Di Gregorio, L. Passamano, Angela Campanella, Liliana Vercelli, Rosa Lomastro, Gessica Vasco, Francesco Danilo Tiziano, Stefania Fiori, Chiara Orsi, Renato Mantegazza, Gian Luca Vita, Gianni Sorarù, Lucia Morandi, Giuseppe Vita, Sonia Messina, Lorena Di Pietro, Tiziano, Fd, Lomastro, R, Di Pietro, L, Pasanisi, Mb, Fiori, S, Angelozzi, C, Abiusi, E, Angelini, C, Sorarù, G, Gaiani, A, Mongini, T, Vercelli, L, Vasco, G, Vita, G, Vita, G. L., Messina, S, Politano, Luisa, Passamano, L, Di Gregorio, Mg, Montomoli, C, Orsi, C, Campanella, A, Mantegazza, R, and Morandi, L.
- Subjects
Male ,Oncology ,Messenger ,Vital Capacity ,SMN1 ,Spinal Muscular Atrophies of Childhood ,Settore MED/03 - GENETICA MEDICA ,Cohort Studies ,Exon ,Range of Motion, Articular ,Genetics (clinical) ,spinal muscular atrophy ,biomarker ,outcome measure ,real-time PCR ,SMN ,Adolescent ,Adult ,Biomarkers ,Biomechanical Phenomena ,Body Weight ,Cross-Sectional Studies ,Female ,Genetic Loci ,Genotype ,Humans ,Middle Aged ,Motor Activity ,RNA, Messenger ,Survival of Motor Neuron 2 Protein ,Young Adult ,Genetics ,SMA ,medicine.anatomical_structure ,Biomarker (medicine) ,Range of Motion ,medicine.medical_specialty ,Biology ,Article ,Internal medicine ,medicine ,Proximal spinal muscular atrophy ,Spinal muscular atrophy ,Motor neuron ,medicine.disease ,nervous system diseases ,Lean body mass ,RNA ,Articular - Abstract
Proximal spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by mutations of the SMN1 gene. Based on severity, three forms of SMA are recognised (types I-III). All patients usually have 2-4 copies of a highly homologous gene (SMN2) which produces insufficient levels of functional survival motor neuron (SMN) protein, due to the alternative splicing of exon 7. The availability of potential candidates to the treatment of SMA has raised a number of issues, including the availability of biomarkers. This study was aimed at evaluating whether the quantification of SMN2 products in peripheral blood is a suitable biomarker for SMA. Forty-five adult type III patients were evaluated by Manual Muscle Testing, North Star Ambulatory Assessment scale, 6-Minute Walk Test, myometry, forced vital capacity, and dual energy X-ray-absorptiometry. Molecular assessments included SMN2 copy number, levels of full length SMN2 (SMN2-fl) transcripts and those lacking exon 7, and SMN protein. Clinical outcome measures strongly correlated to each other. Lean body mass correlated inversely with years from diagnosis and with several aspects of motor performance. SMN2 copy number and SMN protein levels were not associated with motor performance or transcript levels. SMN2-fl levels correlated with motor performance in ambulant patients. Our results indicate that SMN2-fl levels correlate with motor performance only in patients preserving higher levels of motor function, while motor performance was strongly influenced by disease duration and lean body mass. If not taken into account, the confounding effect of disease duration may impair the identification of potential SMA biomarkers.
- Published
- 2012
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