Abstract
Ataxia with oculo-motor apraxia type 2 (AOA2) is a recently described autosomal recessive
cerebellar ataxia (ARCA) caused by mutations in the senataxin gene (SETX).
We analysed the phenotypic spectrum of 19 AOA2 patients with mutations in SETX, which seems to be the third most frequent form of ARCA in Algeria after Freidreich
ataxia and Ataxia with vitamin E deficiency. In AOA2 patients, the mean age at onset
for all families was in the second decade. Cerebellar ataxia was progressive, slowly
leading to disability which was aggravated by axonal polyneuropathy present in almost
all the patients. Mean disease duration until wheelchair was around 20 years. Oculo-motor
apraxia (OMA) was present in 32% of the patients while convergent strabismus was present
in 37%. Strabismus is therefore also very suggestive of AOA2 when associated with
ataxia and polyneuropathy even in the absence of OMA. Cerebellar atrophy was more
severe in the eldest patients; however it may also be an early sign since it was present
in the youngest and paucisymptomatic patients. The initial sign was gait ataxia in
all but two patients who presented with head tremor and writer cramp, respectively.
Serum alpha-fetoprotein, which was elevated in all tested patients, was a good marker
to suggest molecular studies of the SETX gene.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of the Neurological SciencesAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Molecular genetics and familial ataxia.Rev Neurol (Paris). 1993; 149: 698-702
- Ataxia with isolated vitamin E deficiency: heterogeneity of mutations and phenotypic variability in a large number of families.Am J Hum Genet. 1998; 62: 301-310
- Recessive ataxia with ocular apraxia: review of 22 Portuguese patients.Arch Neurol. 2001; 58: 201-205
- Early-onset ataxia with ocular motor apraxia and hypoalbuminemia: the aprataxin gene mutations.Neurology. 2002; 59: 590-595
- Autosomal recessive cerebellar ataxia with oculomotor apraxia (ataxia telangiectasia-like syndrome) is linked to chromosome 9q34.Am J Hum Genet. 2000; 67: 1320-1326
- Homozygosity mapping of spinocerebellar ataxia with cerebellar atrophy and peripheral neuropathy to 9q33–34, and with hearing impairment and optic atrophy to 6p21–23.Eur J Hum Genet. 2000; 8: 986-990
- Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2.Nat Genet. 2004; 36: 225-227
- Senataxin, defective in ataxia oculomotor apraxia type 2, is involved in the defense against oxidative DNA damage.J Cell Biol. 2007; 177: 969-979
- ADCK3, an ancestral kinase, is mutated in a form of recessive ataxia associated with coenzyme Q10 deficiency.Am J Hum Genet. 2008; 82: 661-672
- Diagnostic value of ultrastructural nerve examination in Charcot-Marie-Tooth disease: two CMT 1B cases with pseudo-recessive inheritance.Acta Neuropathol. 2007; 113: 443-449
- Frequency and phenotypic spectrum of ataxia with oculomotor apraxia 2: a clinical and genetic study in 18 patients.Brain. 2004; 127: 759-767
- Mutations in senataxin responsible for Quebec cluster of ataxia with neuropathy.Ann Neurol. 2005; 57: 408-414
- Ataxia with oculomotor apraxia type 2: a clinical, pathologic, and genetic study.Neurology. 2006; 25: 1207-1210
- Modifier genes in mice and humans.Nat Rev Genet. 2001; 2: 165-174
- Clinical and molecular findings of ataxia with oculomotor apraxia type 2 in 4 families.Arch Neurol. 2008; 65: 958-962
Article Info
Publication History
Published online: January 13, 2009
Accepted:
December 2,
2008
Received in revised form:
November 21,
2008
Received:
August 18,
2008
Identification
Copyright
© 2008 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
