title: Ataxia with oculomotor apraxia type 2: a clinical, pathologic, and genetic study.
abstract: BACKGROUND
  Ataxia with oculomotor apraxia type 2 (AOA2) is characterized by onset between age 10 and 22 years, cerebellar atrophy, peripheral neuropathy, oculomotor apraxia (OMA), and elevated serum alpha-fetoprotein (AFP) levels. Recessive mutations in SETX have been described in AOA2 patients.
  
  
  OBJECTIVE
  To describe the clinical features of AOA2 and to identify the SETX mutations in 10 patients from four Italian families.
  
  
  METHODS
  The patients underwent clinical examination, routine laboratory tests, nerve conduction studies, sural nerve biopsy, and brain MRI. All were screened for SETX mutations.
  
  
  RESULTS
  All the patients had cerebellar features, including limb and truncal ataxia, and slurred speech. OMA was observed in two patients, extrapyramidal symptoms in two, and mental impairment in three. High serum AFP levels, motor and sensory axonal neuropathy, and marked cerebellar atrophy on MRI were detected in all the patients who underwent these examinations. Sural nerve biopsy revealed a severe depletion of large myelinated fibers in one patient, and both large and small myelinated fibers in another. Postmortem findings are also reported in one of the patients. Four different homozygous SETX mutations were found (a large-scale deletion, a missense change, a single-base deletion, and a splice-site mutation).
  
  
  CONCLUSIONS
  The clinical phenotype of oculomotor apraxia type 2 is fairly homogeneous, showing only subtle intrafamilial variability. OMA is an inconstant finding. The identification of new mutations expands the array of SETX variants, and the finding of a missense change outside the helicase domain suggests the existence of at least one more functional region in the N-terminus of senataxin.
authors.affiliation: Department of Neurological Sciences, Federico II University, Naples, Italy. sky569@libero.it
authors.forename: C
authors.initials: C
authors.lastname: Criscuolo
authors.forename: L
authors.initials: L
authors.lastname: Chessa
authors.forename: S
authors.initials: S
authors.lastname: Di Giandomenico
authors.forename: P
authors.initials: P
authors.lastname: Mancini
authors.forename: F
authors.initials: F
authors.lastname: Saccà
authors.forename: G S
authors.initials: GS
authors.lastname: Grieco
authors.forename: M
authors.initials: M
authors.lastname: Piane
authors.forename: F
authors.initials: F
authors.lastname: Barbieri
authors.forename: G
authors.initials: G
authors.lastname: De Michele
authors.forename: S
authors.initials: S
authors.lastname: Banfi
authors.forename: F
authors.initials: F
authors.lastname: Pierelli
authors.forename: N
authors.initials: N
authors.lastname: Rizzuto
authors.forename: F M
authors.initials: FM
authors.lastname: Santorelli
authors.forename: L
authors.initials: L
authors.lastname: Gallosti
authors.forename: A
authors.initials: A
authors.lastname: Filla
authors.forename: C
authors.initials: C
authors.lastname: Casali
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D001072:Apraxias / Q000145:classification / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D001259:Ataxia / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D001284:Atrophy; D002531:Cerebellum / Q000473:pathology; D002675:Child, Preschool; D004265:DNA Helicases; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D064251:Multifunctional Enzymes; D009154:Mutation; D015840:Oculomotor Nerve Diseases / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D010375:Pedigree; D010523:Peripheral Nervous System Diseases / Q000235:genetics / Q000473:pathology; D020365:RNA Helicases / Q000235:genetics
chemical_list: D064251:Multifunctional Enzymes; C484368:SETX protein, human; D004265:DNA Helicases; D020365:RNA Helicases