Novel FUS mutations identified through molecular screening in a large cohort of familial and sporadic amyotrophic lateral sclerosis. (15th July 2015)

• Record Type: Journal Article
• Authors: Tarlarini, C.; Lunetta, C.; Mosca, L.; Avemaria, F.; Riva, N.; Mantero, V.; Maestri, E.; Quattrini, A.; Corbo, M.; Melazzini, M. G.; Penco, S.
• Is Part Of: European journal of neurology. Volume 22:Number 11(2015:Nov.)
• Page Start: 1474
• Page End: 1481
• Publication Date: 2015-07-15
• Subjects: Neurology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1111/ene.12772
• Languages: English
• ISSNs: 1351-5101

Abstract

<abstract abstract-type="main" id="ene12772-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ene12772-sec-0001" sec-type="section"> <title>Background and purpose</title> <p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Approximately 5%–10% of cases are familial (FALS) and the remaining are sporadic (SALS). To date FUS mutations are responsible for 4%–6% of familial cases as well as 0.7%–1.8% of sporadic cases.</p> </sec> <sec id="ene12772-sec-0002" sec-type="section"> <title>Methods</title> <p>The frequency of FUS mutations was investigated in an Italian cohort of 500 SALS and 40 FALS patients through direct sequencing of exons 5, 6, 13, 14 and 15.</p> </sec> <sec id="ene12772-sec-0003" sec-type="section"> <title>Results</title> <p>Eight FUS mutation carriers were identified in five SALS (1%) and three FALS (7.5%), five already known and three new mutations: a <italic>de novo</italic> mutation was identified in a sporadic subject as well as the co‐presence of FUS/C9ORF72 mutations in a FALS subject. The molecular and clinical details of the three patients harbouring a novel mutation (G245V, G509D and R491C) are presented here. Moreover the co‐presence of the R491C mutation and C9ORF72 pathological expansion was found according to the oligogenic disease model.</p> </sec> <sec id="ene12772-sec-0004" sec-type="section"> <title>Conclusions</title> <p>In conclusion our results revealed a higher frequency of FUS mutation carriers (7.5%) in FALS compared to literature data together with a higher presence of female gender.</p> </sec> </abstract>