Abstract
BackgroundAutosomal 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.MethodsThis 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).ResultsA 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.ConclusionMutations 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.
Highlights
Autosomal recessive ataxias represent a group of clinically overlapping disorders
Patients with ataxia with oculomotor apraxia type1 (AOA1) present with cerebellar ataxia and oculomotor apraxia between ages 2 and 18 years old [2] accompanied later in life by limb dysmetria and sensory-motor neuropathy which may be associated with dystonia or mental retardation, hypoalbuminemia, hypercholesterolemia and normal immunoglobulins and alpha-fetoprotein levels
We identified a novel truncating mutation R2287X in SETX in one family in addition to the previously reported mutation W210C in MRE11 gene in two families
Summary
Autosomal recessive ataxias represent a group of clinically overlapping disorders These include ataxia with oculomotor apraxia type (AOA1), ataxia with oculomotor apraxia type 2 (AOA2) and ataxia-telangiectasia-like disease (ATLD). Ataxia with Oculomotor Apraxia (AOA) is an autosomal recessive cerebellar ataxia (ARCA) mainly characterized by ataxia, oculomotor apraxia and choeroathetosis [1]. Patients with AOA1 present with cerebellar ataxia and oculomotor apraxia between ages 2 and 18 years old [2] accompanied later in life by limb dysmetria and sensory-motor neuropathy which may be associated with dystonia or mental retardation, hypoalbuminemia, hypercholesterolemia and normal immunoglobulins and alpha-fetoprotein levels. Patients with AOA2 present with gait ataxia, cerebellar atrophy, sensory-motor neuropathy, ocular-motor apraxia and elevated immunoglobulins and alpha-fetoprotein levels with an age of onset (10-22years)[4]. In addition patients with Ataxia-Telangiectasia-Like Disorder (ATLD known as MRE11 ataxia MIM# 604391) present with early onset ataxia and oculomotor apraxia [5]
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