Characterization of the mutation spectrum in a Pakistani cohort of type 3 von Willebrand disease.

INTRODUCTION: Type 3 von Willebrand disease (VWD), a severe autosomal recessive hereditary bleeding disorder, is described by the virtual absence of von Willebrand factor (VWF). In consanguineous populations, for example Pakistan, the disease is reported with a higher incidence rate than the worldwide prevalence. AIMS: This study aims to characterize molecular pathology and clinical profile of type 3 VWD cohort of Pakistani origin. METHODS: In total, 48 patients were enrolled in the current study. Initially, the index patients (IPs) were evaluated by a standardized questionnaire for recording bleeding manifestations and by performing conventional coagulation tests. The diagnosis of VWD type 3 was confirmed by VWF antigens less than 5 IU/dL. Direct sequencing of VWF gene (VWF) was carried out to identify causative gene variations. We evaluated the potential consequence of novel splice site and missense variations by predictive computational programs and in silico structural analysis. RESULTS: VWF mutations were detected in 46 out of 48 IPs (95.8%), predominantly as homozygous variants. In total, twenty-nine different gene defects were characterized in this cohort from which 10 (34.5%) are novel. The majority of the mutations were null alleles (66%; including gene conversions, nonsense, splice site variations, small deletions and insertions), and 34% of them were missense substitutions. CONCLUSION: Herein, we reported for the first time, the pattern of gene defects in Pakistani type 3 VWD cohort. We identified a wide heterogeneous mutation spectrum along with variability in the type of bleeding episodes.

Designing an Assistive Learning Aid for Writing Acquisition: A Challenge for Children with Dyslexia.

In Pakistan, the biggest challenge is to provide high quality education to the individuals with learning disabilities. Besides the well known affordance issue, there is a lack of awareness regarding the term dyslexia and remedial teaching training that causes the identification as well as remediation of the dyslexic individuals at early stages in Pakistan. The research was focused to exploit the benefits of using the modern mobile technology features in providing a learning platform for young dyslexic writers. Based on potential usability requirements of young dyslexic writers stated by remedial teachers of dyslexics, an android based application is designed and implemented using the usability engineering process model to encourage the learning process and help dyslexic children improve their fundamental handwriting skill. In addition, a handwriting learning algorithm based on concepts of machine learning is designed and implemented to decide the learning content, evaluate the learning performance, display the performance results and record the learning growth to show the strengths and weaknesses of a dyslexic child. The research was also aimed to assess the usability of the learner-centered application by the targeted population by conducting a user acceptance test to evaluate their learning experience and benefits of the developed application to dyslexic users. The results of the evaluation provided by the participants revealed that application has potential benefits to foster the learning process and help children with dyslexia by improving their foundational writing skills.