Introduction: High repeat expansion (HRE) alleles in C9orf72 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 C9orf72 repeats in healthy elderly from the Italian population. Methods: 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 C9orf72 Kit (Asuragen, Inc.), using standardized protocols that have been validated through blind proficiency testing. Results: All samples carried hexanucleotide G(4)C(2) 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. Conclusion: This study describes the distribution of hexanucleotide G(4)C(2) 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.

Distribution of the C9orf72 hexanucleotide repeat expansion in healthy subjects: a multicenter study promoted by the Italian IRCCS network of neuroscience and neurorehabilitation / 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. - In: FRONTIERS IN NEUROLOGY. - ISSN 1664-2295. - ELETTRONICO. - 15:(2024), pp. 1284459.0-1284459.0. [10.3389/fneur.2024.1284459]

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

Nacmias, Benedetta;Bagnoli, Silvia;Ingannato, Assunta;
2024

Abstract

Introduction: High repeat expansion (HRE) alleles in C9orf72 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 C9orf72 repeats in healthy elderly from the Italian population. Methods: 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 C9orf72 Kit (Asuragen, Inc.), using standardized protocols that have been validated through blind proficiency testing. Results: All samples carried hexanucleotide G(4)C(2) 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. Conclusion: This study describes the distribution of hexanucleotide G(4)C(2) 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.
2024
15
0
0
Goal 3: Good health and well-being
Giardina, Emiliano; Mandich, Paola; Ghidoni, Roberta; Ticozzi, Nicola; Rossi, Giacomina; Fenoglio, Chiara; Tiziano, Francesco Danilo; Esposito, Federi...espandi
File in questo prodotto:
File Dimensione Formato  
giardina.pdf

accesso aperto

Tipologia: Pdf editoriale (Version of record)
Licenza: Open Access
Dimensione 740.7 kB
Formato Adobe PDF
740.7 kB Adobe PDF

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1353476
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 2
  • ???jsp.display-item.citation.isi??? 2
social impact