Abstract
Amyotrophic lateral sclerosis (ALS) is as an adult-onset neurodegenerative disorder involving both upper and lower motor neurons. About 5% of all cases exhibit signs of frontotemporal degeneration (FTD). We established the mutation frequency of C9ORF72, SOD1, TARDBP, and FUS genes in 307 patients with sporadic ALS, 46 patients with familial ALS (FALS), and 73 patients affected with FTD, all originating from the northeastern part of Italy. C9ORF72 pathogenic expansion was found on 22% of familial ALS, 5% of sporadic ALS, and 14% of FTD patients, resulting the most frequently genetic determinant in our cohort. Sequence analysis of ALS cohort identified 2 novel variants on SOD1 (p.Glu41Gly) and FUS (p.Gly496Glyfs*31). Interestingly, the single base deletion on FUS was observed in an homozygous state, suggesting a recessive pattern of inheritance. No point mutations were identified on FTD cohort. Although useful to direct genetic testing, this study results expand the current knowledge of ALS genetics.
| Original language | English |
|---|---|
| Journal | Neurobiology of Aging |
| Volume | 35 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2014 |
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Keywords
- ALS
- C9ORF72
- FTD
- FUS
- Genetic screening
- SOD1
- TARDBP
ASJC Scopus subject areas
- Clinical Neurology
- Neuroscience(all)
- Ageing
- Developmental Biology
- Geriatrics and Gerontology
Cite this
Improving the knowledge of amyotrophic lateral sclerosis genetics : Novel SOD1 and FUS variants. / Bertolin, Cinzia; D'Ascenzo, Carla; Querin, Giorgia; Gaiani, Alessandra; Boaretto, Francesca; Salvoro, Cecilia; Vazza, Giovanni; Angelini, Corrado; Cagnin, Annachiara; Pegoraro, Elena; Sorarù, Gianni; Mostacciuolo, Maria Luisa.
In: Neurobiology of Aging, Vol. 35, No. 5, 05.2014.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Improving the knowledge of amyotrophic lateral sclerosis genetics
T2 - Novel SOD1 and FUS variants
AU - Bertolin, Cinzia
AU - D'Ascenzo, Carla
AU - Querin, Giorgia
AU - Gaiani, Alessandra
AU - Boaretto, Francesca
AU - Salvoro, Cecilia
AU - Vazza, Giovanni
AU - Angelini, Corrado
AU - Cagnin, Annachiara
AU - Pegoraro, Elena
AU - Sorarù, Gianni
AU - Mostacciuolo, Maria Luisa
PY - 2014/5
Y1 - 2014/5
N2 - Amyotrophic lateral sclerosis (ALS) is as an adult-onset neurodegenerative disorder involving both upper and lower motor neurons. About 5% of all cases exhibit signs of frontotemporal degeneration (FTD). We established the mutation frequency of C9ORF72, SOD1, TARDBP, and FUS genes in 307 patients with sporadic ALS, 46 patients with familial ALS (FALS), and 73 patients affected with FTD, all originating from the northeastern part of Italy. C9ORF72 pathogenic expansion was found on 22% of familial ALS, 5% of sporadic ALS, and 14% of FTD patients, resulting the most frequently genetic determinant in our cohort. Sequence analysis of ALS cohort identified 2 novel variants on SOD1 (p.Glu41Gly) and FUS (p.Gly496Glyfs*31). Interestingly, the single base deletion on FUS was observed in an homozygous state, suggesting a recessive pattern of inheritance. No point mutations were identified on FTD cohort. Although useful to direct genetic testing, this study results expand the current knowledge of ALS genetics.
AB - Amyotrophic lateral sclerosis (ALS) is as an adult-onset neurodegenerative disorder involving both upper and lower motor neurons. About 5% of all cases exhibit signs of frontotemporal degeneration (FTD). We established the mutation frequency of C9ORF72, SOD1, TARDBP, and FUS genes in 307 patients with sporadic ALS, 46 patients with familial ALS (FALS), and 73 patients affected with FTD, all originating from the northeastern part of Italy. C9ORF72 pathogenic expansion was found on 22% of familial ALS, 5% of sporadic ALS, and 14% of FTD patients, resulting the most frequently genetic determinant in our cohort. Sequence analysis of ALS cohort identified 2 novel variants on SOD1 (p.Glu41Gly) and FUS (p.Gly496Glyfs*31). Interestingly, the single base deletion on FUS was observed in an homozygous state, suggesting a recessive pattern of inheritance. No point mutations were identified on FTD cohort. Although useful to direct genetic testing, this study results expand the current knowledge of ALS genetics.
KW - ALS
KW - C9ORF72
KW - FTD
KW - FUS
KW - Genetic screening
KW - SOD1
KW - TARDBP
UR - http://www.scopus.com/inward/record.url?scp=84893749133&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84893749133&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2013.10.093
DO - 10.1016/j.neurobiolaging.2013.10.093
M3 - Article
C2 - 24325798
AN - SCOPUS:84893749133
VL - 35
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
IS - 5
ER -