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INTRODUCTION: Autosomal recessive cerebellar ataxias (ARCA) comprise a phenotypically and genetically heterogeneous group of diseases. Recently, a subgroup of ARCA associated with oculomotor apraxia has been delineated. STATE OF THE ART: The ataxias with oculomotor apraxia (AOA) include four distinct genetic entities at least: ataxia-telangiectasia, ataxia telangiectasia-like disorder, ataxia with oculomotor apraxia type 1 (AOA1) and type 2 (AOA2). The responsible genes, ATM, MRE11, APTX and SETX respectively, are implicated in DNA-break repair mechanisms. CONCLUSION: We describe the phenotypic and genetic characteristics of these ataxias, based on a review of the literature and a personal study of AOA1 and AOA2 patients. 相似文献
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We report a case of vertical ocular motor apraxia in a 4-year old boy whom we have followed for 2 years. The patient had no upward and downward voluntary movements of the eyes since birth, but horizontal movements were normal. He achieved gaze changes in the vertical plane by combined blinks and head movements. Magnetic resonance imaging demonstrated bilateral lesions at the mesencephalic-diencephalic junction. 相似文献
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Autosomal recessive cerebellar ataxias (ARCAs) are a phenotypically and genetically heterogeneous group of diseases. Recently,
a subgroup of ARCA associated with oculomotor apraxia (AOA) has been delineated. It includes at least four distinct genetic
entities: ataxia-telangiectasia, ataxia-telangiectasia-like disorder, and ataxia with oculomotor apraxia type 1 (AOA1) and
type 2 (AOA2). The phenotypes share several similarities, and the responsible genes, ATM, MRE11, APTX, and SETX, respectively, are all implicated in DNA break repair. As in many other DNA repair deficiencies, neurodegeneration is a hallmark
of these diseases. Recently, the genes for two new autosomal recessive cerebellar ataxias with oculomotor apraxia, AOA1 and
AOA2, were identified. Here, we report the phenotypic characteristics, genetic characteristics, and the recent advances concerning
AOA1 and AOA2. 相似文献
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Mahajnah M Basel-Vanagaite L Inbar D Kornreich L Weitz R Straussberg R 《Journal of child neurology》2005,20(6):523-525
Ataxia with oculomotor apraxia is an autosomal recessive inherited disease characterized by childhood onset of progressive cerebellar ataxia, oculomotor apraxia, and progressive motor peripheral neuropathy. The mean age at onset is approximately 4.7 years, with oculomotor apraxia appearing a few years later. Diagnosis is based on molecular genetic analysis for mutations of the aprataxin (APTX) gene (chromosome 9p13.1; ataxia with oculomotor apraxia 1). Ataxia with oculomotor apraxia 2 is caused by an unknown gene mutation at locus 9q34. We describe two siblings, born to consanguineous parents, who had clinical features of cerebellar ataxia, tremor, dysarthria, oculomotor apraxia, and motor peripheral neuropathy. Brain magnetic resonance imaging showed cerebellar atrophy and mild brainstem atrophy. Electromyography showed signs of axonal neuropathy. The molecular genetic analysis demonstrated the APTX mutation W279X at locus 9p13.3 (ataxia with oculomotor apraxia 1 disease), and psychologic studies showed mild cognitive impairment. We suggest that mentation can be compromised in ataxia with oculomotor apraxia 1. 相似文献
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M Vercelletto-Friol F Lavenant J H Bricout T Venisse P Vercelletto J R Feve 《Revue neurologique》1986,142(2):140-144
A 7 year-old child with congenital oculomotor apraxia (Cogan's syndrome) presented with mainly voluntary horizontal saccadic movements. Fixation of a visual target could be obtained only by a sudden movement of the head preceded by eyelid blinking. Electro-oculography confirmed the predominant disturbance of saccadic movements (delay in onset, hypometria). CT scan showed agenesis of the corpus callosum and atrophy of the vermis together with enlargement of the 4th ventricle and pre-pontine cisternae. The role of these anomalies in the pathogenesis of this rare congenital syndrome of good prognosis is discussed. 相似文献
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Salvatore E Varrone A Criscuolo C Mancini P Sansone V Strisciuglio C Cicala D Scarano V Salvatore M Pappatà S De Michele G Filla A 《Journal of neurology》2008,255(1):45-48
Ataxia with oculomotor
apraxia type 1 (AOA1) is a rare
autosomal recessive neurodegenerative
disease, recently associated
with mutations in the aprataxin
gene. Main features are early onset
cerebellar ataxia, oculomotor
apraxia and peripheral neuropathy.
The presence of choreoathetosis or
dystonia in some patients suggests
basal ganglia involvement, but
these structures appear preserved
in a single case in which neuropathological
examination was
performed. To evaluate in vivo the
nigrostriatal function we studied
dopamine transporter (DAT)
density with [123I] 2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FPCIT)-SPECT in four AOA1 patients
and eight healthy volunteers. All
patients showed ataxia and neuropathy;
only one had chorea and
none had dystonia. Comparing
with controls, AOA1 patients
showed a slight reduction of the
average striatal DAT density, which
was bilateral and uniform in caudate
and putamen. Nigrostriatal
impairment occurred even in the
absence of extrapyramidal features.
Our data suggest subclinical
involvement of basal ganglia in
AOA1. 相似文献
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José Gazulla MD Isabel Benavente MD Isabel Pérez López‐Fraile MD Pedro Modrego MD Michel Koenig MD 《Muscle & nerve》2009,40(3):481-485
Two siblings with ataxia with oculomotor apraxia type 2 (AOA2) exhibited electrophysiological findings suggestive of a sensorimotor neuronopathy, and primary ovarian failure was detected in one of them. Genetic analysis disclosed a novel, homozygous frameshift mutation in the senataxin gene, 2755_2756delGT, responsible for a premature stop codon at position 2760. It is suggested that a neuronopathy might cause the neuromuscular disturbance in AOA2, and that ovarian failure should be looked for in female patients with the disease. Muscle Nerve, 2009 相似文献
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Early-onset ataxia with oculomotor apraxia and hypoalbuminemia is an autosomal recessive cerebellar ataxia characterized by oculomotor apraxia, peripheral neuropathy, and hypoalbuminemia. Mutations in aprataxin gene located at chromosome 9q13 have been identified recently in Japanese and European patients. This study reports two cases of siblings with early-onset ataxia with oculomotor apraxia and hypoalbuminemia, which manifested early onset before 2 years of age with relatively rapid progression and severe dystonia. Both of the siblings were compound heterozygotes with aprataxin gene mutations, 689 insT and G692A, in exon 5 that encodes the histidine triad domain of the aprataxin protein. The novel missense mutation, G692A, was not present in 40 unrelated and unaffected individuals. 相似文献
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Le Ber I Dubourg O Benoist JF Jardel C Mochel F Koenig M Brice A Lombès A Dürr A 《Neurology》2007,68(4):295-297
APTX gene mutations responsible for ataxia-oculomotor apraxia 1 (AOA1) were identified in a family previously reported with ataxia and coenzyme Q10 (CoQ10) deficiency. We measured muscle CoQ10 levels in six patients with AOA1 and found decreased levels in five. Patients homozygous for the W279X mutation had lower values (p = 0.003). A therapeutic trial of CoQ10 may be warranted in patients with AOA1. 相似文献
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The authors describe four siblings from consanguineous parents who presented with oculomotor deficit in early childhood characterized by impaired volitional horizontal saccades, compensatory lateral head thrust, and preservation of vertical movement. When about 10 years of age, heavily calcified aortic and mitral valves required surgery. Fibroblast beta-glucocerebrosidase activity was markedly reduced. Genotype analysis indicated that the two patients who were tested were homozygous for the D409H (1342G-->C) mutation. Relating this rare phenotype of Gaucher disease to D409H mutation will facilitate management of the disease and counseling of families. 相似文献
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Criscuolo C Mancini P Saccà F De Michele G Monticelli A Santoro L Scarano V Banfi S Filla A 《Neurology》2004,63(11):2173-2175
Ataxia with oculomotor apraxia type 1 (AOA1) is an autosomal recessive disorder characterized by early-onset cerebellar ataxia, oculomotor apraxia, and peripheral neuropathy. The causative gene (APTX) has been recently identified in Portuguese and Japanese kindreds. Three patients with AOA1 were identified in an APTX mutation screening on 28 Southern Italian patients with progressive ataxia and peripheral neuropathy. A novel homozygous missense mutation (H201Q) was found in one patient and a Japanese missense mutation (P206L) in two. AOA1 clinical heterogeneity and onset later than previously described are shown. 相似文献
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Ataxia and oculomotor apraxia are seen in ataxia-telangiectasia, type 1 ataxia with oculomotor apraxia, and type 2 ataxia with oculomotor apraxia; however, only type 1 ataxia with oculomotor apraxia is associated with aprataxin gene mutation. We report two American children, a sister and a brother, with type 1 ataxia with oculomotor apraxia and aprataxin gene mutations and briefly review type 1 ataxia with oculomotor apraxia. 相似文献
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《Journal of clinical neuroscience》2014,21(9):1627-1631
Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive cerebellar ataxia associated with mutations in SETX, which encodes the senataxin protein, a DNA/RNA helicase. We describe the clinical phenotype and molecular characterization of a Colombian AOA2 patient who is compound heterozygous for a c.994 C>T (p.R332W) missense mutation in exon 7 and a c.6848_6851delCAGA (p.T2283KfsX32) frameshift deletion in SETX exon 21. Immunocytochemistry of patient-derived fibroblasts revealed a normal cellular distribution of the senataxin protein, suggesting that these mutations do not lead to loss or mis-localization of the protein, but rather that aberrant function of senataxin underlies the disease pathogenesis. Furthermore, we used the alkaline comet assay to demonstrate that patient-derived fibroblast cells exhibit an increased susceptibility to oxidative DNA damage. This assay provides a novel and additional means to establish pathogenicity of SETX mutations. 相似文献