Vijayalakshmi Perumalsamy

Mutational Screening of LCA Genes Emphasizing RPE65 in South Indian Cohort of Patients

Background Leber congenital amaurosis (LCA) is the most severe form of inherited retinal visual impairment in children. So far, mutations in more than 20 genes have been known to cause LCA and among them, RPE65 is a suitable candidate for gene therapy. The mutational screenings of RPE65 and other LCA genes are requisite in support of emerging gene specific therapy for LCA. Therefore, we have carried out a comprehensive LCA genes screening using a combined approach of direct sequencing and DNA microarray based Asper chip analysis. Methodology/Principal Findings Thirty clinically diagnosed index LCA cases from Southern India were screened for coding and flanking intronic regions of RPE65 through direct sequencing. Among thirty, 25 cases excluded from RPE65 mutations were subjected to Asper chip analysis, testing 784 known pathogenic variations in 15 major LCA genes. In RPE65 screening, four different pathogenic variations including two novel (c.361insT & c.939T>A) and two known (c.394G>A & c.361delT) mutations were identified in five index cases. In the chip analysis, seven known pathogenic mutations were identified in six index cases, involving genes GUCY2D, RPGRIP1, AIPL1, CRX and IQCB1. Overall, 11 out of 30 LCA cases (36.6%) revealed pathogenic variations with the involvement of RPE65 (16.6%), GUCY2D (10%), RPGRIP1 (3.3%), AIPL1 (3.3%) and CRX & IQCB1 (3.3%). Conclusions/Significance Our study suggests that such combined screening approach is productive and cost-effective for mutation detection and can be applied in Indian LCA cohort for molecular diagnosis and genetic counselling.

Analysis of the SALL4 gene in patients with Duane retraction syndrome in a South Indian population.

Duane retraction syndrome (DRS) is a congenital eye movement disorder characterized most typically by partial or complete failure of abduction and narrowing of palpebral fissure with globe retraction on adduction. Recently mutations of the SALL4 gene on chromosome 20 have been linked to DRS associated with radial forearm malformations (Okihiro syndrome). In this prospective, non-interventional study we screened for SALL4 mutations in 72 patients clinically diagnosed as having isolated DRS or DRS associated syndromes. All four exonic and the neighboring intronic regions of SALL4 gene were amplified by sixteen sets of primers using polymerase chain reaction and were subjected to bi-directional sequencing and BLAST analysis. No genetic variations were detected in the coding region and in the neighboring intronic regions of the SALL4 gene suggesting an alternative mechanism in the pathogenesis of these disorders in the South Indian population.

Molecular Genetic Testing for Carrier-Prenatal Diagnosis and Computational Analysis of Oculocutaneous Albinism Type 1

Molecular Genetic Testing for Carrier- Prenatal Diagnosis and Computational Analysis of Oculocutaneous Albinism Type 1 In India epidemiological-communicable diseases are on the decline due to better living conditions and healthcare delivery in the society. On the other hand, the relative increase in the prevalence of genetic diseases threatens to be a public health problem. One such group of metabolic disorder is Albinism. General population based oculocutaneous albinism (OCA) carrier screening is controversial in all the races. Because of the occurrence of this disease in prior generations, it is necessary to create the knowledge, so that even uneducated affected family members will be willing to diagnose the disease status. As a result, the carrier detection in general population has become necessary in Indian population.

Functional and cognitive vision assessment in children with autism spectrum disorder

PURPOSE To assess functional vision in children with autism spectrum disorder (ASD) with a cognitive visual function battery in addition to standard ophthalmic examinations. METHODS Subjects were recruited from a school for children with ASD. In addition to a comprehensive ophthalmic examination, all children underwent cognitive vision assessment at a tertiary ophthalmological care center in India. RESULTS A total of 30 children were included. The distribution of the number of children with mild to moderate versus severe ASD was nearly equal based on CARS autism scores. The majority of subjects had normal color vision (16/18), contrast (24), shape discrimination (26), and perception of directionality (28). Most were not able to identify optical illusions or differentiate tests of emotions. Ocular pursuits, saccades, and recognition of size differences were often abnormal. Poor visual closure was noted in (11) subjects. The duration of fixation to Heidi face target was inversely proportional to the severity of ASD. The study further established that cognitive visual impairment was present in children with ASD irrespective of their severity of ASD. CONCLUSIONS All subjects had some form of cognitive visual impairment independent of ASD severity.