Assessment of Candidate Loci in Neurological diseases

在过去的一段时间里，我们研究了各种神经系统疾病中的PRKN， PINK， APP, PS1, PS2， PRNP， PGRN和ATXN2/3突变。我们继续在脊髓小脑共济失调方面的工作，通过在一个大队列中确定我们发现的SCA15突变的频率，并通过使用自合子作图对我们发现的尚未发表的SCA位点进行随访。此外，我们继续与NINDS和NHGRI的合作者合作，以确定哪些患者有LRRK2突变，并可以前瞻性地参与我们的合作研究，跟踪这些患者及其尚未受影响的家庭成员。

In the last period we have worked on PRKN, PINK, APP, PS1, PS2, PRNP, PGRN and ATXN2/3 mutations in varied neurological diseases. We have continued our work in spinocerebellar ataxias by establishing the frequency of SCA15 mutations identified by us in a large cohort and by follow up of as yet unpublished SCA loci identified by us using autozygosity mapping. In addition we continue to work with our collaborators at NINDS and NHGRI to establish which of our patients have LRRK2 mutations and can be enrolled in our collaborative study following these patients and their as yet unaffected family members prospectively. In addition this year we have performed an assessment of APOE variability in Parkinson's disease, as all previous studies provided somewhat unclear results. This work involved analysis of the common coding variants (epsilon types) in APOE in a very large cohort of PD patients (this work is currently under review). We have also performed an assessment of candidate loci for recessive ataxia in a series of patients from Tunisia who have ataxia. This work allows us to parse such families into those with known mutations, and those that should be prioritized for further genetic work aimed at finding new genetic causes of disease.