Mutational Analysis of Known ALS Genes in an Italian Population-Based Cohort.

Neurology
Maurizio GrassanoAmerican Genomic Center

Abstract

To assess the burden of rare genetic variants and to estimate the contribution of known amyotrophic lateral sclerosis (ALS) genes in an Italian population-based cohort, we performed whole genome sequencing in 959 patients with ALS and 677 matched healthy controls. We performed genome sequencing in a population-based cohort (Piemonte and Valle d'Aosta Registry for ALS [PARALS]). A panel of 40 ALS genes was analyzed to identify potential disease-causing genetic variants and to evaluate the gene-wide burden of rare variants among our population. A total of 959 patients with ALS were compared with 677 healthy controls from the same geographical area. Gene-wide association tests demonstrated a strong association with SOD1, whose rare variants are the second most common cause of disease after C9orf72 expansion. A lower signal was observed for TARDBP, proving that its effect on our cohort is driven by a few known causal variants. We detected rare variants in other known ALS genes that did not surpass statistical significance in gene-wise tests, thus highlighting that their contribution to disease risk in our cohort is limited. We identified potential disease-causing variants in 11.9% of our patients. We identified the genes most frequ...Continue Reading

References

Jul 24, 2001·Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders : Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases·B R BrooksUNKNOWN World Federation of Neurology Research Group on Motor Neuron Diseases
Feb 14, 2009·PLoS Genetics·Bo Eskerod Madsen, Sharon R Browning
Oct 8, 2009·Genetic Epidemiology·Andrew P Morris, Eleftheria Zeggini
Jul 9, 2011·American Journal of Human Genetics·Michael C WuXihong Lin
Sep 3, 2011·American Journal of Human Genetics·Dan-Yu Lin, Zheng-Zheng Tang
Oct 27, 2012·Neurology·Adriano ChiòUNKNOWN PARALS
Dec 27, 2013·Nature Neuroscience·Alan E RentonBryan J Traynor
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Aug 25, 2015·Journal of Neurology, Neurosurgery, and Psychiatry·Petra SteinackerMarkus Otto
Jul 12, 2017·JAMA Neurology·Adriano ChiòUNKNOWN Piemonte and Valle d’Aosta Register for ALS (PARALS)
Apr 2, 2018·Trends in Genetics : TIG·Hung Phuoc NguyenJulie van der Zee

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Citations

Sep 28, 2021·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration·Kristiana SalmonAngela Genge
Sep 30, 2021·Journal of Neurology, Neurosurgery, and Psychiatry·Antonio CanosaAdriano Chio

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