Details

Autor(en) / Beteiligte

• Origone, Paola
• Caponnetto, Claudia
• Mantero, Vittorio
• Cichero, Elena
• Fossa, Paola
• Geroldi, Alessandro
• Verdiani, Simonetta
• Bellone, Emilia
• Mancardi, Gianluigi
• Mandich, Paola

Titel

Fast course ALS presenting with vocal cord paralysis: Clinical features, bioinformatic and modelling analysis of the novel SOD1 Gly147Ser mutation

Ist Teil von

• Amyotrophic lateral sclerosis, 2012-01, Vol.13 (1), p.144-148

Ort / Verlag

England: Informa Healthcare

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• Abstract In this report we describe a novel SOD1 mutation (Gly147Ser) in an Italian sporadic ALS patient. The patient presented with hoarseness due to bilateral vocal cord paralysis and a rapid clinical course. Mutational analysis of the SOD1 gene was carried out by direct sequencing. In silico bioinformatics analysis and molecular modelling was used to analyse the SOD1 function modifications produced by the mutated residue. A heterozygous c.442 G > A transition, which leads to a change at codon 147 resulting in a serine rather than glycine, was found in the patient. Bioinformatics analysis and molecular modelling strongly suggest a dramatic effect of Gly147Ser mutation on SOD1 function. In conclusion, Gly147Ser represent a new missense mutation whose effect may correlate with the peculiar clinical bulbar phenotype onset with bilateral vocal cord paresis and rapid clinical course of the disease. Ethical and psychological dilemmas about genetic testing in apparently sporadic subjects are still matter of debate.