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Autosomal recessive cerebellar ataxias are a group of clinically and genetically heterogeneous neurodegenerative disorders. Growing data have shown that there is difficulty with genetic counseling in a deeply consanguineous population because of the presence of genetic heterogeneity in patients sharing similar phenotypes. The objective of this study was to report on 11 Tunisian patients belonging to the same large consanguineous family and sharing autosomal recessive ataxia phenotypes caused by three distinct gene defects. A large consanguineous Tunisian family with 11 affected patients was selected. All patients had a complete neurological examination. Blood samples were collected for molecular study. Mutation analysis revealed the presence of three distinct gene defects in the FXN (FRDA), TTPA (AVED), and SACS (ARSACS) genes within the same large family. The genetic heterogeneity observed in this family drew attention to the difficulty of genetic counseling in an inbred population and to the need for genotyping all affected members before giving genetic counseling. [ABSTRACT FROM AUTHOR]

Background: Several genes have been implicated in the pathogenesis of Parkinson's disease (PD). The aim of this study was to define the clinical symptoms and age-associated cumulative incidence of the most frequent mutation associated with PD, LRRK2 Gly2019Ser. Methods: 238 patients with sporadic PD and 371 unrelated control participants from the Arab-Berber population were screened at the Institut National de Neurologie, Tunis. Symptoms of PD were assessed using the Hoehn and Yahr scale, the unified Parkinson's disease rating scale, and the Epworth scale. Genotyping for LRRK2 6055G-->A, which causes the Gly2019Ser mutation, was done in all participants, and the age-specific cumulative incidence of PD was calculated by Kaplan-Meier analysis. Findings: 30% of patients with PD in this case-control sample were carriers of LRRK2 Gly2019Ser. The age of onset of symptoms and the clinical presentation of patients with LRRK2 Gly2019Ser were similar to those of patients with idiopathic PD. Carriers of LRRK2 Gly2019Ser were 22.6 times (95% CI 10.2-50.1) more likely to be affected by PD than non-carriers. Tremor was the predominant symptom in LRRK2 Gly2019Ser carriers (92% [homozygotes] vs 75% [heterozygotes] vs 69% [non-carriers]; Cochran-Armitage trend test p=0.0587). Disease severity, response to treatment, and disease duration were similar among LRRK2 Gly2019Ser homozygotes, heterozygotes, and non-carriers (p=0.85). Disease penetrance in LRRK2 Gly2019Ser carriers ranged from less than 20% in those younger than 50 years to greater than 80% at 70 years. Interpretation: The LRRK2 Gly2019Ser mutation in patients with PD is a useful aid to diagnosis. LRRK2 Gly2019Ser penetrance can vary but in most carriers PD seems an inevitable consequence of ageing. LRRK2 Gly2019Ser considerably increases susceptibility to neuronal degeneration, although the process might be mediated by many triggers. By contrast, idiopathic PD is rare before 50 years and the prevalence only increases to 4% in the oldest members of the population. Funding: GlaxoSmithKline; National Institutes of Health; and Mayo Foundation. [ABSTRACT FROM AUTHOR]