TY - JOUR
T1 - The Rise of the GRN C157KfsX97 Mutation in Southern Italy
T2 - Going Back to the Fall of the Western Roman Empire
AU - Coppola, Cinzia
AU - Saracino, Dario
AU - Oliva, Mariano
AU - Puoti, Gianfranco
AU - Lus, Giacomo
AU - Le Ber, Isabelle
AU - Pariente, Jérémie
AU - Tessitore, Alessandro
AU - Benussi, Luisa
AU - Ghidoni, Roberta
AU - Carrara, Matteo
AU - Ricci, Martina
AU - Redaelli, Veronica
AU - Tiraboschi, Pietro
AU - Caroppo, Paola
AU - Giaccone, Giorgio
AU - Bonavita, Simona
AU - Rossi, Giacomina
N1 - Funding Information:
The research leading to these results has received funding from the Italian Ministry of Health, “Ricerca Corrente”, to Fondazione IRCCS Istituto Neuro-logico Carlo Besta (GR, MR) and to IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli (LB, RG, MC).
Publisher Copyright:
© 2020 - IOS Press and the authors. All rights reserved.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - Background: Frontotemporal lobar degeneration (FTLD) designates a group of neurodegenerative diseases with remarkable clinical, pathological, and genetic heterogeneity. Mutations in progranulin gene (GRN) are among the most common causes of familial FTLD. The GRN C157KfsX97 mutation is the most frequent mutation occurring in Southern Italy and has been already described in a previous work. Objective: In this study, we reported on additional cases carrying the same mutation and performed a genetic study on the whole cohort, aiming at demonstrating the existence of a founder effect and estimating the age of this mutation. Methods/Results: Based on the haplotype sharing analysis, a founder effect was highly probable, while the age of the mutation, estimated by means of DMLE+ software, resulted in a range between 52 and 82 generations, with the highest frequency at about 62 generations, 1,550 years ago. Conclusion: This is the first study that reports the age estimation of the most recent common ancestor for the GRN C157KfsX97 mutation recurring in Southern Italy. Mutation dating in a geographically restricted population may be useful in order to plan genetic counseling and screening programs in the field of public health.
AB - Background: Frontotemporal lobar degeneration (FTLD) designates a group of neurodegenerative diseases with remarkable clinical, pathological, and genetic heterogeneity. Mutations in progranulin gene (GRN) are among the most common causes of familial FTLD. The GRN C157KfsX97 mutation is the most frequent mutation occurring in Southern Italy and has been already described in a previous work. Objective: In this study, we reported on additional cases carrying the same mutation and performed a genetic study on the whole cohort, aiming at demonstrating the existence of a founder effect and estimating the age of this mutation. Methods/Results: Based on the haplotype sharing analysis, a founder effect was highly probable, while the age of the mutation, estimated by means of DMLE+ software, resulted in a range between 52 and 82 generations, with the highest frequency at about 62 generations, 1,550 years ago. Conclusion: This is the first study that reports the age estimation of the most recent common ancestor for the GRN C157KfsX97 mutation recurring in Southern Italy. Mutation dating in a geographically restricted population may be useful in order to plan genetic counseling and screening programs in the field of public health.
KW - Common founder
KW - frontotemporal lobar degeneration
KW - GRN
KW - haplotype
KW - mutation
KW - mutation dating
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U2 - 10.3233/JAD-200924
DO - 10.3233/JAD-200924
M3 - Article
C2 - 33016921
AN - SCOPUS:85095135281
VL - 78
SP - 387
EP - 394
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
SN - 1387-2877
IS - 1
ER -