title: The SETX missense variation spectrum as evaluated in patients with ALS4-like motor neuron diseases.
abstract: Mutations in the senataxin (SETX) gene can cause amyotrophic lateral sclerosis 4 (ALS4), an autosomal dominant form of juvenile onset amyotrophic lateral sclerosis, or result in autosomal recessive ataxia with oculomotor apraxia type 2. Great caution regarding the possible disease causation, especially of missense variations, has to be taken. Here, we evaluated the significance of all previously reported SETX missense mutations as well as six newly identified variations in 54 patients suspected of having ALS4. Yet, epidemiologic and in silico evidence indicates that all newly identified variations and two previously published ALS4-related missense variations (C1554G and I2547T) are most likely non-pathogenic, demonstrating the problems of interpretation of SETX missense alleles in the absence of functional assays.
authors.affiliation: Department of Human Genetics, Ruhr University, 44780 Bochum, Germany. larissa.arning@rub.de
authors.forename: Larissa
authors.initials: L
authors.lastname: Arning
authors.forename: Jörg T
authors.initials: JT
authors.lastname: Epplen
authors.forename: Elisa
authors.initials: E
authors.lastname: Rahikkala
authors.forename: Corinna
authors.initials: C
authors.lastname: Hendrich
authors.forename: Albert C
authors.initials: AC
authors.lastname: Ludolph
authors.forename: Anne-Dorte
authors.initials: AD
authors.lastname: Sperfeld
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D004265:DNA Helicases; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000235:genetics; D064251:Multifunctional Enzymes; D020125:Mutation, Missense / Q000502:physiology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D020365:RNA Helicases / Q000235:genetics*
chemical_list: D064251:Multifunctional Enzymes; C484368:SETX protein, human; D004265:DNA Helicases; D020365:RNA Helicases