Identification of novel Angiogenin (ANG) gene missense variants in German patients with amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease characterized by the selective death of motor neurons in the motor cortex, brain stem and spinal cord. Recently, missense variants in the angiogenin gene (ANG), an angiogenic factor expressed in ventral horn motor neurons that is up-regulated by hypoxia, have been found in ALS patients of Irish/Scottish, North American, Italian, French and Dutch descent. To investigate the role of ANG in the German population, we screened for mutations by sequencing the entire coding region of the ANG gene in a large sample of 581 German ALS cases and 616 sex- and age-matched healthy controls. We identified two heterozygous missense variants, F(-13)L and K54E, in two German sporadic ALS cases but not in controls. Both missense variants are novel and have not been previously found in ALS cases. Our results suggest that missense variants in the ANG gene play a role in ALS in the German population and provide further evidence to support the hypothesis that angiogenic factors up-regulated by hypoxia are involved in the pathophysiology of ALS.
Fernández-Santiago
Rubén
R
Department for Neurodegenerative Disorders, Hertie Institute for Clinical Brain Research, Eberhard-Karls University, Tuebingen, Germany.
Hoenig
Sabine
S
Lichtner
Peter
P
Sperfeld
Anne-Dorte
AD
Sharma
Manu
M
Berg
Daniela
D
Weichenrieder
Oliver
O
Illig
Thomas
T
Eger
Katharina
K
Meyer
Thomas
T
Anneser
Johanna
J
Münch
Christoph
C
Zierz
Stephan
S
Gasser
Thomas
T
Ludolph
Albert
A
D000690:Amyotrophic Lateral Sclerosis / Q000208:ethnology / Q000235:genetics*; D002490:Central Nervous System / Q000378:metabolism / Q000503:physiopathology; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D005858:Germany / Q000208:ethnology; D006579:Heterozygote; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D018384:Oxidative Stress / Q000235:genetics; D012259:Ribonuclease, Pancreatic / Q000235:genetics*; D044465:White People
D005819:Genetic Markers; C046366:angiogenin; D012259:Ribonuclease, Pancreatic