Aprataxin Gene Mutations in Tunisian Families

Institut National de Neurologie, Département de Biologie Moléculaire et de Neuropathologie,CNRS/INSERM Université Louis Pasteur, Illkirch, CHU de Strasbourg, France.
Neurology (Impact Factor: 8.29). 10/2004; 63(5):928-9. DOI: 10.1212/01.WNL.0000137044.06573.46
Source: PubMed


The authors report clinical and genetic study of 13 patients from three unrelated Tunisian families with an early onset cerebellar ataxia associated with oculomotor apraxia. Cerebellar ataxia with oculomotor apraxia 1 (AOA1) represents a clinically heterogeneous disease caused by mutations in the aprataxin gene. Two novel mutations were identified, the complete deletion of the gene, which seems to not correlate with an increased severity of the disease, and a splice mutation on the acceptor splice site of exon 7.

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    • "This leads to oculomotor apraxia, a condition that is characterized by the inability to make side-to-side eye movements.[8] The literature has described various types of genetic mutations associated with the APTX gene leading to AOA1 including substitution, missense and splicing mutations;[9–12] however, the IVS4-12delT mutation has never been specifically reported. This may play a major role in the observed oculomotor symptoms and may also be the cause of the abnormal visual evoked potentials seen in our patient. "
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    ABSTRACT: Ataxia, although rare, can be a symptom of many debilitating movement disorders. Hereditary ataxias are one subset of this condition and manifest when there is a genetic abnormality involved. Ataxia oculomotor apraxia type 1 (AOA1), an autosomal recessive ataxia, results from a mutation on the aprataxin gene (APTX). We characterized a novel homozygous deletion mutation (IVS4-12delT) on the APTX gene in a 14-year-old male born to consanguineous parents. This case report emphasizes the importance of investigating and increasing awareness of novel genetic mutations in order to help diagnose and further classify hereditary ataxias.
    Full-text · Article · Apr 2013 · Annals of Indian Academy of Neurology
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    • "were identified in patients with AOA1. These include; missense, nonsense, splice mutations, single base insertions and deletions [2,6-9]. A deletion of the whole APTX ORF was reported in one family with AOA1 phenotype [6]. "
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    ABSTRACT: Background Autosomal recessive ataxias represent a group of clinically overlapping disorders. These include ataxia with oculomotor apraxia type1 (AOA1), ataxia with oculomotor apraxia type 2 (AOA2) and ataxia-telangiectasia-like disease (ATLD). Patients are mainly characterized by cerebellar ataxia and oculomotor apraxia. Although these forms are not quite distinctive phenotypically, different genes have been linked to these disorders. Mutations in the APTX gene were reported in AOA1 patients, mutations in SETX gene were reported in patients with AOA2 and mutations in MRE11 were identified in ATLD patients. In the present study we describe in detail the clinical features and results of genetic analysis of 9 patients from 4 Saudi families with ataxia and oculomotor apraxia. Methods This study was conducted in the period between 2005-2010 to clinically and molecularly characterize patients with AOA phenotype. Comprehensive sequencing of all coding exons of previously reported genes related to this disorder (APTX, SETX and MRE11). Results A novel nonsense truncating mutation c.6859 C > T, R2287X in SETX gene was identified in patients from one family with AOA2. The previously reported missense mutation W210C in MRE11 gene was identified in two families with autosomal recessive ataxia and oculomotor apraxia. Conclusion Mutations in APTX , SETX and MRE11 are common in patients with autosomal recessive ataxia and oculomotor apraxia. The results of the comprehensive screening of these genes in 4 Saudi families identified mutations in SETX and MRE11 genes but failed to identify mutations in APTX gene.
    Full-text · Article · Feb 2011 · BMC Medical Genetics
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    • "The proband showed shortrapid movements in her fingers, but was able to control them, challenging their choreic origin. Third, mental retardation or cognitive impairment are common in Japanese and French patients [2] [3] manifesting a dysexecutive syndrome related to dysfunction of the front-cerebellar pathways [3]; the proband did not disclosed mental retardation or cognitive impairment similarly to Portuguese and Tunisian patients [12] [13]. Fourth, some authors consider the presence of Babinski sign a distinctive trait of FRDA as to AOA [3]. "
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    ABSTRACT: Ataxia oculomotor apraxia type 1 (AOA1) is the most common form of autosomal recessive ataxia in Japan, and the second in Portugal after Friedreich ataxia. AOA1 is typically characterized by early-onset cerebellar ataxia, oculomotor apraxia, hypoalbuminemia, hypercholesterolemia and late axonal sensori-motor neuropathy. AOA1 is associated with the aprataxin gene (APTX) encoding a protein involved in DNA repair. We characterized a novel homozygous missense mutation of APTX in a 34 year-old female patient born from consanguineous parents. The mutation, a Val230Gly caused by a c.689 T>G substitution, involved the histidine-triad (HIT) domain of the protein, affected a phylogenetically conserved amino acid and was absent in the control population. We described the clinical and neurophysiological features, the findings at structural and functional brain imaging, and the pathological picture of the sural nerve biopsy. The report emphasized the genetical and phenotypical heterogeneity of AOA1 by demonstrating atypical features such as absence of oculomotor apraxia and signs of pyramidal involvement. Expression studies by Western blotting on fibroblasts demonstrated that the homozygous Val230Gly mutation was associated with decreased levels of APTX indicating a loss-of-function mechanism.
    Full-text · Article · Oct 2007 · Journal of the Neurological Sciences
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