Analysis of normal C9orf72 repeat length as possible disease modifier in amyotrophic lateral sclerosis.

Autor:	Peverelli S; Department of Neurology-Laboratory of Neuroscience, IRCCS, Istituto Auxologico Italiano, Milan, Italy., Brusati A; Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy., Casiraghi V; Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy, and., Sorce MN; Department of Neurology-Laboratory of Neuroscience, IRCCS, Istituto Auxologico Italiano, Milan, Italy., Invernizzi S; Department of Neurology-Laboratory of Neuroscience, IRCCS, Istituto Auxologico Italiano, Milan, Italy., Santangelo S; Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy, and., Morelli C; Department of Neurology-Laboratory of Neuroscience, IRCCS, Istituto Auxologico Italiano, Milan, Italy., Verde F; Department of Neurology-Laboratory of Neuroscience, IRCCS, Istituto Auxologico Italiano, Milan, Italy.; 'Dino Ferrari' Center, Dept. of Pathophysiology and Transplantation, University of Milan, Milan, Italy., Silani V; Department of Neurology-Laboratory of Neuroscience, IRCCS, Istituto Auxologico Italiano, Milan, Italy.; 'Dino Ferrari' Center, Dept. of Pathophysiology and Transplantation, University of Milan, Milan, Italy., Ticozzi N; Department of Neurology-Laboratory of Neuroscience, IRCCS, Istituto Auxologico Italiano, Milan, Italy.; 'Dino Ferrari' Center, Dept. of Pathophysiology and Transplantation, University of Milan, Milan, Italy., Ratti A; Department of Neurology-Laboratory of Neuroscience, IRCCS, Istituto Auxologico Italiano, Milan, Italy.; Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy, and.
Jazyk:	angličtina
Zdroj:	Amyotrophic lateral sclerosis & frontotemporal degeneration [Amyotroph Lateral Scler Frontotemporal Degener] 2024 Feb; Vol. 25 (1-2), pp. 207-210. Date of Electronic Publication: 2024 Jan 23.
DOI:	10.1080/21678421.2023.2273965
Abstrakt:	The C9orf72 hexanucleotide repeat (HR) expansion is the main genetic cause of amyotrophic lateral sclerosis (ALS), with expansion size from 30 to >4000 units. Normal C9orf72 HR length is polymorphic (2-23 repeats) with alleles >8 units showing a low frequency in the general population. This study aimed to investigate if the normal C9orf72 HR length influences C9orf72 gene expression and acts as disease modifier in ALS patients negative for C9orf72 mutation (ALS-C9Neg). We found that the distribution of HR alleles was similar in 325 ALS-C9Neg and 303 healthy controls. Gene expression analysis in blood revealed a significant increase of total C9orf72 and V3 mRNA levels in ALS-C9Neg carrying two long alleles (L/L; ≥8 units) compared to patients homozygous for the 2-unit short allele (S/S). However, HR allele genotypes (L/L, S/L, S/S) correlated with no clinical parameters. Our data suggest that normal C9orf72 HR length does not act as disease modifier in ALS-C9Neg despite increasing gene expression.
Databáze:	MEDLINE
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