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Anshuman Verma, Sundaresan Periasamy, Vijayalakshmi Perumalsamy; A Novel Insertional RPE65 Mutation in Southern Indian Cohort of Leber Congenital Amaurosis (LCA) Patients. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2382.
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Leber congenital amaurosis (LCA) is a most severe form of visual impairment found in infants and children. At present around 15 genes have been reported for disease causing mutations. The RPE65, one of these genes accounts for around 6% of LCA cases globally.The genetic spectrum of RPE65 mutation is essentially required in support of emerging gene therapy treatment. Therefore, in order to know the mutational spectrum of RPE65 in southern Indian cohort we screened 15 clinically well diagnosed LCA cases.
Direct PCR and sequencing were used to screen 14 exons along with the immediately flanking intronic sequences of RPE65 gene in 15 LCA cases. In addition 50 ethnically matched healthy control samples were sequenced to validate the pathogenic nature of variations.
A novel homozygous thymine insertional mutation at c.361 (c.361insT) in exon5 was identified in one patient. This insertion was not detected in 50 control samples. Parental DNA analysis demonstrated the mutation in heterozygous condition. This change predicts a frame shift at position 120th amino acid onwards leading to truncated protein formation of RPE65. The same patient also harbors an intronic polymorphism G/C (rs1925955). Four other LCA cases showed the presence of exonic polymorphism c.1056G>A (rs12145904). The affected patient presented visual impairment since birth associated with fixed dilated pupil and nystagmus. Fundus examination revealed white pigmentation in the mid periphery with attenuated vessels. ERG pattern shown flat photopic and scotopic waves.The patient did not represent any other systemic abnormalities.
To the best of our knowledge the c.361insT mutation has not been described before. Our results shows RPE65 mutations contribute to 6% of LCA cases in southern Indian cohort. Screening of more number of samples with aid of high throughput sequencing method is under investigation.
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