TY - JOUR
T1 - Novel Splice-Site Mutation in SMN1 Associated with a very Severe SMA-I Phenotype
AU - Ronchi, Dario
AU - Previtali, Stefano Carlo
AU - Sora, Maria Grazia Natali
AU - Barera, Graziano
AU - Del Menico, Benedetta
AU - Corti, Stefania
AU - Bresolin, Nereo
AU - Comi, Giacomo Pietro
PY - 2015/5/1
Y1 - 2015/5/1
N2 - Spinal muscular atrophy (SMA) is a genetic disorder characterized by degeneration of motor neurons and muscle weakness and atrophy. The majority of patients harbor homozygous SMN1 deletions, resulting in an SMN1-null genotype. A variable number of copies of SMN2, the centromeric copy of SMN1, fails to compensate for the absence of SMN1 but can act as a modifier. Less than 5 % of patients with SMA display intragenic mutations on the second allele, detectable by direct sequencing. The effects of these mutations are not easily predictable, hindering a clear correlation with the clinical phenotype. We describe a novel SMN1 mutation that affected the donor splice site of exon 7 and resulted in an unusually severe SMA phenotype with rapid fatal outcome in an Italian infant.
AB - Spinal muscular atrophy (SMA) is a genetic disorder characterized by degeneration of motor neurons and muscle weakness and atrophy. The majority of patients harbor homozygous SMN1 deletions, resulting in an SMN1-null genotype. A variable number of copies of SMN2, the centromeric copy of SMN1, fails to compensate for the absence of SMN1 but can act as a modifier. Less than 5 % of patients with SMA display intragenic mutations on the second allele, detectable by direct sequencing. The effects of these mutations are not easily predictable, hindering a clear correlation with the clinical phenotype. We describe a novel SMN1 mutation that affected the donor splice site of exon 7 and resulted in an unusually severe SMA phenotype with rapid fatal outcome in an Italian infant.
KW - Motor neuron disorder
KW - Spinal muscular atrophy
KW - Splice site mutation
KW - Survival motor neuron
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U2 - 10.1007/s12031-014-0483-4
DO - 10.1007/s12031-014-0483-4
M3 - Article
C2 - 25572663
AN - SCOPUS:84939987019
VL - 56
SP - 212
EP - 215
JO - Journal of Molecular Neuroscience
JF - Journal of Molecular Neuroscience
SN - 0895-8696
IS - 1
ER -