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

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.

Key words::

• ALS
• SOD1
• genetics
• mutation

Acknowledgements

This work was partly supported by grant ‘La sclerosi laterale amiotrofica (SLA) e le gravi malattie del motoneurone: dai meccanismi molecolari alla presa in carico del paziente’ from Regione Liguria to GLM and PM. The authors are grateful to patients and their families for participation in the studies and ongoing support.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.