A Novel Homozygous Variant of SETX Causes Ataxia with Oculomotor Apraxia Type 2

BACKGROUND AND PURPOSE: Autosomal recessive cerebellar ataxias constitute a highly heterogeneous group of neurodegenerative disorders. This study was carried out to determine the clinical and genetic causes of ataxia in two families from Pakistan. METHODS: Detailed clinical investigations were carried out on probands in two consanguineous families. Magnetic resonance imaging was performed. Exome sequencing data were examined for likely pathogenic variants. Candidate variants were checked for cosegregation with the phenotype using Sanger sequencing. Public databases including ExAC, GnomAD, dbSNP, and the 1,000 Genome Project as well as ethnically matched controls were checked to determine the frequencies of the alleles. Conservation of missense variants was ensured by aligning orthologous protein sequences from diverse vertebrate species. RESULTS: Reverse phenotyping identified spinocerebellar ataxia, autosomal recessive 1 [OMIM 606002, also referred to as ataxia oculomotor apraxia type 2 (AOA2)] and ataxia telangiectasia (OMIM 208900) in the two families. A novel homozygous missense mutation c.202 C>T (p.Arg68Cys) was identified within senataxin, SETX in the DNA of both patients in one of the families with AOA2. The patients in the second family were homozygous for a known variant in ataxia-telangiectasia mutated (ATM) gene: c.7327 C>T (p.Arg2443Ter). Both variants were absent from 100 ethnically matched control chromosomes and were either absent or present at very low frequencies in the public databases. CONCLUSIONS: This report extends the allelic heterogeneity of SETX mutations causing AOA2 and also presents an asymptomatic patient with a pathogenic ATM variant.

Possibility of thrombolytic therapy in acute thrombotic stroke in Services Hospital Lahore

Objective: to find Public awareness regarding stroke and the cause of delayed presentation of stroke patients in our setup at Services Hospital Lahore

Material and Methods: this prospective study was conducted on 113 patients in Department of Neurology, Services Hospital, and Lahore over a period of one year from January, 2012 to December, 2012. The time of presentation was divided into 4 segments; within 6 hours of stroke onset, within 6-12 hours of stroke onset, within 12-24 hours of stroke onset and more than 24 hours of stroke onset with diagnosis of cerebral infarction. Also knowledge of patients regarding tPA and cause of delay was assessed

Results: there were 68 males and 45 females with age range of 27 to 83 years. Only 9 patients presented within 6 hours, 22 within 6-12 hours, 4 7 within 12-24 hours and 35 more than 24 hours. A very little percentage of patients with cerebral infarction landed in Emergency department within 6 hours of stroke onset. Also 91.1 % of patients were unaware of thrombolytic therapy. When asked for a single factor for pre-hospital delay, 67% of patients labelled transportation issues as a cause

Conclusion: because early presentation is a prerequisite for thrombolysis for acute ischemic stroke we recommend to start educational programs that increase public awareness of the need to seek medical help promptly after stroke and word stroke should be replaced with brain attack and measures to improve the traffic sense should also be undertaken