Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper and lower motor neurons. The hexanucleotide repeatexpansioninC9orf72gene(C9orf72-HRE)isthemostfrequentgeneticcauseofALS.SincemanyALSpedigreesshowed incomplete penetrance, several genes have been analyzed as possible modifiers. Length of the GCG repeat tract in NIPA1 (nonimprinted in Prader-Willi/Angelman syndrome 1) gene has been recently investigated as a possible modifier factor for C9orf72HRE patientswith contrasting findings.To disclosethe possiblerole ofNIPA1GCG repeatlengthasmodifierofthedisease risk inC9orf72-HREcarriers,weanalyzedalargecohortof532ItalianALScasesenrichedinC9orf72-HREcarriers(172cases)and 483Italiancontrols.Thissamplesizeispowered(92%power,p=0.05)toreplicatethemodifiereffectobservedinliterature.We didnotobservehigherfrequencyofNIPA1longalleles(>8GCG)inC9orf72-HREcarriers(3.5%)comparedwithC9orf72-HRE negativepatients(4.1%)andhealthycontrols(5%).Forthelattercomparison,wemeta-analyzedourdatawithcurrentlyavailable literature data, and no statistically significant effect was observed (p=0.118). In conclusion, we did not confirm a role ofNIPA1 repeat length as a modifier of the C9orf72 ALS disease risk.

Analysis of the GCG repeat length in NIPA1 gene in C9orf72-mediated ALS in a large Italian ALS cohort

Brunetti M.;Barberis M.;Bersano E.;Calvo A.;Moglia C.;Chio A.;
2019

Abstract

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper and lower motor neurons. The hexanucleotide repeatexpansioninC9orf72gene(C9orf72-HRE)isthemostfrequentgeneticcauseofALS.SincemanyALSpedigreesshowed incomplete penetrance, several genes have been analyzed as possible modifiers. Length of the GCG repeat tract in NIPA1 (nonimprinted in Prader-Willi/Angelman syndrome 1) gene has been recently investigated as a possible modifier factor for C9orf72HRE patientswith contrasting findings.To disclosethe possiblerole ofNIPA1GCG repeatlengthasmodifierofthedisease risk inC9orf72-HREcarriers,weanalyzedalargecohortof532ItalianALScasesenrichedinC9orf72-HREcarriers(172cases)and 483Italiancontrols.Thissamplesizeispowered(92%power,p=0.05)toreplicatethemodifiereffectobservedinliterature.We didnotobservehigherfrequencyofNIPA1longalleles(>8GCG)inC9orf72-HREcarriers(3.5%)comparedwithC9orf72-HRE negativepatients(4.1%)andhealthycontrols(5%).Forthelattercomparison,wemeta-analyzedourdatawithcurrentlyavailable literature data, and no statistically significant effect was observed (p=0.118). In conclusion, we did not confirm a role ofNIPA1 repeat length as a modifier of the C9orf72 ALS disease risk.
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https://link.springer.com/journal/10072
ALS; C9orf72-HRE carriers; NIPA1
Corrado L.; Brunetti M.; Di Pierro A.; Barberis M.; Croce R.; Bersano E.; De Marchi F.; Zuccala M.; Barizzone N.; Calvo A.; Moglia C.; Mazzini L.; Chio A.; D'Alfonso S.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1720147
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