Distribution of the C9orf72 hexanucleotide repeat expansion in healthy subjects: a multicenter study promoted by the Italian IRCCS network of neuroscience and neurorehabilitation

High repeat expansion (HRE) alleles in have been linked to both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD); ranges for intermediate allelic expansions have not been defined yet, and clinical interpretation of molecular data lacks a defined genotype-phenotype association. I...

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Published in:	Frontiers in neurology Vol. 15; p. 1284459
Main Authors:	Giardina, Emiliano, Mandich, Paola, Ghidoni, Roberta, Ticozzi, Nicola, Rossi, Giacomina, Fenoglio, Chiara, Tiziano, Francesco Danilo, Esposito, Federica, Capellari, Sabina, Nacmias, Benedetta, Mineri, Rossana, Campopiano, Rosa, Di Pilla, Luana, Sammarone, Federica, Zampatti, Stefania, Peconi, Cristina, De Angelis, Flavio, Palmieri, Ilaria, Galandra, Caterina, Nicodemo, Eleonora, Origone, Paola, Gotta, Fabio, Ponti, Clarissa, Nicsanu, Roland, Benussi, Luisa, Peverelli, Silvia, Ratti, Antonia, Ricci, Martina, Di Fede, Giuseppe, Magri, Stefania, Serpente, Maria, Lattante, Serena, Domi, Teuta, Carrera, Paola, Saltimbanco, Elisa, Bagnoli, Silvia, Ingannato, Assunta, Albanese, Alberto, Tagliavini, Fabrizio, Lodi, Raffaele, Caltagirone, Carlo, Gambardella, Stefano, Valente, Enza Maria, Silani, Vincenzo
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 2024
Subjects:	allele distribution amyotrophic lateral sclerosis C9orf72 frontotemporal dementia GGGGCC hexanucleotide repeat Neurology frontotemporal dementia GGGGCC hexanucleotide repeat allele distribution amyotrophic lateral sclerosis C9orf72
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Summary:	High repeat expansion (HRE) alleles in have been linked to both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD); ranges for intermediate allelic expansions have not been defined yet, and clinical interpretation of molecular data lacks a defined genotype-phenotype association. In this study, we provide results from a large multicenter epidemiological study reporting the distribution of repeats in healthy elderly from the Italian population. A total of 967 samples were collected from neurologically evaluated healthy individuals over 70 years of age in the 13 institutes participating in the RIN (IRCCS Network of Neuroscience and Neurorehabilitation) based in Italy. All samples were genotyped using the AmplideXPCR/CE Kit (Asuragen, Inc.), using standardized protocols that have been validated through blind proficiency testing. All samples carried hexanucleotide G C expansion alleles in the normal range. All samples were characterized by alleles with less than 25 repeats. In particular, 93.7% of samples showed a number of repeats ≤10, 99.9% ≤20 repeats, and 100% ≤25 repeats. This study describes the distribution of hexanucleotide G C expansion alleles in an Italian healthy population, providing a definition of alleles associated with the neurological healthy phenotype. Moreover, this study provides an effective model of federation between institutes, highlighting the importance of sharing genomic data and standardizing analysis techniques, promoting translational research. Data derived from the study may improve genetic counseling and future studies on ALS/FTD.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Mamede De Carvalho, University of Lisbon, Portugal Reviewed by: Marta Gromicho, Universidade de Lisboa, Portugal; Wilson Marques, University of São Paulo, Brazil
ISSN:	1664-2295 1664-2295
DOI:	10.3389/fneur.2024.1284459