Mutations of the ANG gene in French patients with sporadic amyotrophic lateral sclerosis.
BACKGROUND
Mutations in the angiogenin gene, ANG, have been associated recently with familial and sporadic forms of amyotrophic lateral sclerosis (ALS). However, the cellular and molecular mechanisms that link ANG, a multidomain protein, to ALS are still unknown.


OBJECTIVE
To assess the frequency of ANG gene mutations in 855 French patients with sporadic ALS.


METHODS
We analyzed by direct sequencing the full coding region of the ANG gene in a cohort of French patients with sporadic ALS. The clinical characteristics of patients carrying ANG mutations are detailed.


METHODS
French ALS Study Group. Patients A total of 855 patients with sporadic ALS.


METHODS
Results of genetic analyses.


RESULTS
We observed a previously identified mutation (pI46V) in 2 patients with ALS without a known family link and found a novel mutation (pR121H) in 1 patient who developed ALS with rapid progression. We did not observe an association between patients with ALS and the rs11701 polymorphism, as previously reported in certain ALS populations of other ethnic origins.


CONCLUSIONS
Overall, our findings support the implication of ANG gene mutations as a rare but widespread cause of ALS.
Paubel
Agathe
A
INSERM U930, Université François Rabelais Tours, CHRU de Tours, Faculté de Médecine, 10 boulevard Tonnellé, BP3223, 37032 Tours CEDEX, France.
Violette
Jeremy
J
Amy
Maïté
M
Praline
Julien
J
Meininger
Vincent
V
Camu
William
W
Corcia
Philippe
P
Andres
Christian R
CR
Vourc'h
Patrick
P
D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D020134:Catalytic Domain / Q000235:genetics; D002490:Central Nervous System / Q000378:metabolism / Q000503:physiopathology; D015331:Cohort Studies; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D005602:France / Q000453:epidemiology; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D012259:Ribonuclease, Pancreatic / Q000097:blood / Q000235:genetics*
D005819:Genetic Markers; C046366:angiogenin; D012259:Ribonuclease, Pancreatic