title: Clinical and molecular findings of ataxia with oculomotor apraxia type 2 (AOA2) in 5 Tunisian families.
abstract: Ataxia with oculomotor apraxia type 2 (AOA2) is a recently described autosomal recessive cerebellar ataxia caused by mutations in the SETX gene. It is a rare monogenic disease characterized by progressive cerebellar ataxia, oculomotor apraxia, axonal sensorimotor neuropathy, and an elevated serum α-fetoprotein level. To date, >100 AOA2 patients have been described and 75 different mutations in the SETX gene have been identified. We report here the clinical and genetic findings of 13 AOA2 patients from 5 unrelated Tunisian consanguineous families. DNA was collected from probands and available family members, and the 24 SETX exons were screened by direct sequencing. Four different homozygous SETX gene mutations were identified. The missense mutation 915G>T [W305C] has been described previously in Algeria. The 3 other SETX mutations are novel, including a missense mutation c.7231C>T [R 2380 W], a nonsense mutation c.6475 C>T [R2098X], and a deletion c.7180-7183delAAAA [D2332fsX2343]. More extensive screening by molecular genetic analysis of SETX in patients with Friedreich ataxia-like phenotype may show that AOA2 is more common in Tunisia than previously thought.
authors.affiliation: National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. benhamadm@mail.nih.gov
authors.forename: Monia Benhamed
authors.initials: MB
authors.lastname: Hammer
authors.forename: Ghada
authors.initials: G
authors.lastname: El Euch-Fayache
authors.forename: Houda
authors.initials: H
authors.lastname: Nehdi
authors.forename: Dalel
authors.initials: D
authors.lastname: Saidi
authors.forename: Amira
authors.initials: A
authors.lastname: Nasri
authors.forename: Fatma
authors.initials: F
authors.lastname: Nabli
authors.forename: Yosr
authors.initials: Y
authors.lastname: Bouhlal
authors.forename: Wieme
authors.initials: W
authors.lastname: Maamouri-Hicheri
authors.forename: Fayçal
authors.initials: F
authors.lastname: Hentati
authors.forename: Rim
authors.initials: R
authors.lastname: Amouri
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D002648:Child; D018389:Codon, Nonsense; D003241:Consanguinity; D004265:DNA Helicases; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D064251:Multifunctional Enzymes; D009154:Mutation; D020125:Mutation, Missense; D020365:RNA Helicases / Q000235:genetics*; D020754:Spinocerebellar Ataxias / Q000151:congenital; D013132:Spinocerebellar Degenerations / Q000453:epidemiology / Q000235:genetics*; D014416:Tunisia / Q000453:epidemiology; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; D064251:Multifunctional Enzymes; C484368:SETX protein, human; D004265:DNA Helicases; D020365:RNA Helicases