title: Analysis of the C9orf72 gene in spinal muscular atrophy patients.
abstract: Spinal muscular atrophy and amyotrophic lateral sclerosis are both motor neuron disorders. Several studies have tried to establish a link between the two diseases but the subject is still under debate. In amyotrophic lateral sclerosis, large expansions of the hexanucleotide GGGGCC in intron 1 of the C9orf72 gene are responsible for a variable percentage of familial and sporadic cases. We investigated whether the number of the hexanucleotide repeat in C9orf72 was associated with the phenotype and the number of SMN2 copies in a group of 162 SMA patients. Conventional PCR, repeat primed-PCR and Southern blot were used to determine repeat number and characterize large expansions. Results showed that no pathological (> 30 repeats) or premutated alleles (20-30 repeats) were found. The allelic distribution of the C9orf72 gene in spinal muscular atrophy patients overlapped with the data obtained in our control population, discarding putative repeats that may be associated with the disease. No association was observed with either the SMA phenotype or the number of SMN2 copies. In conclusion, the involvement of C9orf72 as a genetic modifier in spinal muscular atrophy is unlikely. Current investigation of modifier genes in SMA and of the link between ALS and SMA should consider other possible candidates.
authors.affiliation: Servei de Genètica, Hospital de la Santa Creu i Sant Pau , Barcelona.
authors.forename: Laura
authors.initials: L
authors.lastname: Alías
authors.forename: Sara
authors.initials: S
authors.lastname: Bernal
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Barceló
authors.forename: Rebeca
authors.initials: R
authors.lastname: Martínez-Hernández
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Martínez
authors.forename: Montserrat
authors.initials: M
authors.lastname: Baiget
authors.forename: Eduardo F
authors.initials: EF
authors.lastname: Tizzano
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics; D000073885:C9orf72 Protein; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics; D055540:Survival of Motor Neuron 2 Protein / Q000235:genetics
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins; C526471:SMN1 protein, human; C526477:SMN2 protein, human; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein
keywords: Spinal muscular atrophy; amyotrophic lateral sclerosis; chromosome 9 open reading frame 72 gene (C9orf72); repeat-primed PCR