TY - JOUR
T1 - G41S SOD1 mutation
T2 - A common ancestor for six ALS Italian families with an aggressive phenotype
AU - Battistini, Stefania
AU - Ricci, Claudia
AU - Giannini, Fabio
AU - Calzavara, Silvia
AU - Greco, Giuseppe
AU - Del Corona, Alberto
AU - Mancuso, Michelangelo
AU - Battistini, No
AU - Siciliano, Gabriele
AU - Carrera, Paola
PY - 2010
Y1 - 2010
N2 - More than 140 different mutations have been reported in the Cu/Zn superoxide dismutase-1 (SOD1) gene in patients with amyotrophic lateral sclerosis (ALS), some occurring as founder mutations. Occasionally, specific mutations are associated with a particular phenotype. We evaluated a possible genotype-phenotype correlation and looked for a founder effect in nine patients from six unrelated families with ALS, all carrying the G41S mutation, originating from north-west Tuscany in central Italy. Mutational analysis of the SOD1 gene was carried out by direct sequencing. A haplotype study was carried out using eight polymorphic markers flanking the SOD1 gene. The clinical pattern of the nine familial ALS (FALS) patients was characterized by spinal onset with early upper and lower motor neuron involvement, appearance of bulbar signs within one year, and death a few months later. Mean age at onset was 49.3 years and mean duration of disease was 0.9 years. Genotyping revealed a common haplotype for the G41S allele. We provide the first evidence that the G41S mutation in Italy originates from a common founder. In addition, our findings strengthen the data reported previously and indicate that the G41S mutation is consistently associated with a uniform and dramatic, fast-progressing phenotype.
AB - More than 140 different mutations have been reported in the Cu/Zn superoxide dismutase-1 (SOD1) gene in patients with amyotrophic lateral sclerosis (ALS), some occurring as founder mutations. Occasionally, specific mutations are associated with a particular phenotype. We evaluated a possible genotype-phenotype correlation and looked for a founder effect in nine patients from six unrelated families with ALS, all carrying the G41S mutation, originating from north-west Tuscany in central Italy. Mutational analysis of the SOD1 gene was carried out by direct sequencing. A haplotype study was carried out using eight polymorphic markers flanking the SOD1 gene. The clinical pattern of the nine familial ALS (FALS) patients was characterized by spinal onset with early upper and lower motor neuron involvement, appearance of bulbar signs within one year, and death a few months later. Mean age at onset was 49.3 years and mean duration of disease was 0.9 years. Genotyping revealed a common haplotype for the G41S allele. We provide the first evidence that the G41S mutation in Italy originates from a common founder. In addition, our findings strengthen the data reported previously and indicate that the G41S mutation is consistently associated with a uniform and dramatic, fast-progressing phenotype.
KW - Amyotrophic lateral sclerosis
KW - Haplotype
KW - Phenotype-genotype correlation
KW - SOD1
UR - http://www.scopus.com/inward/record.url?scp=77649282136&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77649282136&partnerID=8YFLogxK
U2 - 10.3109/17482960902995592
DO - 10.3109/17482960902995592
M3 - Article
C2 - 19488901
AN - SCOPUS:77649282136
VL - 11
SP - 210
EP - 215
JO - Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders
JF - Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders
SN - 1466-0822
IS - 1-2
ER -