Ataxia with oculomotor apraxia type 2: novel mutations in six patients with juvenile age of onset and elevated serum alpha-fetoprotein.
Ataxia with oculomotor apraxia type 2 (AOA2), a neurodegenerative disorder with juvenile to adolescent onset is caused by mutations within the SENATAXIN gene ( SETX). We performed molecular analyses in six patients showing clinically an AOA2 phenotype and moderate to significant elevated serum alpha-fetoprotein levels. Sequencing the 24 coding exons and flanking intronic sequences revealed 11 novel DNA variations, including seven unknown missense mutations, a dinucleotide deletion, a four-nucleotide deletion affecting the 5' splice site of exon 22 and two sequence variations, which are considered to be polymorphisms. By molecular testing the clinical diagnosis has been confirmed in all patients.
Bernard
V
V
Institut für Humangenetik, Universität zu Lübeck, Lübeck, Germany. veronica.bernard@uk-sh.de
Stricker
S
S
Kreuz
F
F
Minnerop
M
M
Gillessen-Kaesbach
G
G
Zühlke
C
C
D000293:Adolescent; D000328:Adult; D000483:Alleles; D001072:Apraxias / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D001284:Atrophy; D002524:Cerebellar Ataxia / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D002531:Cerebellum / Q000473:pathology; D002872:Chromosome Deletion; D003241:Consanguinity; D004265:DNA Helicases; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D064251:Multifunctional Enzymes; D020125:Mutation, Missense; D009460:Neurologic Examination; D015840:Oculomotor Nerve Diseases / Q000097:blood / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D020365:RNA Helicases / Q000235:genetics*; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000378:metabolism*
D064251:Multifunctional Enzymes; D000509:alpha-Fetoproteins; C484368:SETX protein, human; D004265:DNA Helicases; D020365:RNA Helicases