Dhandayuthapani Sudha1,2, Aparna Ganapathy3, Puja Mohan3, Ashraf U Mannan3, Shuba Krishna3, Srividya Neriyanuri4, Meenakshi Swaminathan5, Pukhraj Rishi6, Subbulakshmi Chidambaram7, Jayamuruga Pandian Arunachalam8,9. 1. SN ONGC Department of Genetics and Molecular Biology, Vision Research Foundation, 41, College Road, Nungambakkam, Chennai, 600006, India. 2. School of Biotechnology, SASTRA University, Thanjavur, India. 3. Strand Life Sciences, Hebbal, Bengaluru, India. 4. Elite School of Optometry, Unit of Medical Research Foundation, Chennai, India. 5. Department of Pediatric Ophthalmology, Medical Research Foundation, Chennai, India. 6. Shri Bhagwan Mahavir Vitreo-Retinal Services, Sankara Nethralaya, Medical Research Foundation, Chennai, India. 7. R.S. Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Chennai, India. 8. SN ONGC Department of Genetics and Molecular Biology, Vision Research Foundation, 41, College Road, Nungambakkam, Chennai, 600006, India. ajmpandian@gmail.com. 9. Central Inter-Disciplinary Research Facility (CIDRF), Sri Balaji Vidyapeeth University, Mahatma Gandhi Medical College and Research Institute Campus, Pondicherry, India. ajmpandian@gmail.com.
Abstract
PURPOSE: NDP-related retinopathies are a group of X-linked disorders characterized by degenerative and proliferative changes of the neuroretina, occasionally accompanied with varying degrees of mental retardation and sensorineural hearing loss. NDP is the predominant gene associated with NDP-related retinopathies. The purpose of this study was to report the clinical and genetic findings in three unrelated patients diagnosed with NDP-related retinopathies. METHODS: The patients underwent complete ophthalmic examination followed by genetic analyses. NDP gene was screened by direct sequencing approach. Targeted resequencing of several other ocular genes was carried out in patient samples that either indicated NDP gene deletion or tested negative for NDP mutation. Gene quantitation analysis was performed using real-time PCR. RESULTS: The whole NDP gene was deleted in patient I, while a missense NDP mutation, c.205T>C, was identified in patient II, and both had classical Norrie disease ocular phenotype (with no other systemic defects). Patient III who was diagnosed with familial exudative vitreoretinopathy did not show any mutation in the known candidate genes as well as in other ocular genes tested. CONCLUSIONS: The patient with whole NDP gene deletion did not exhibit any apparent extraocular defects (like mental retardation or sensorineural hearing loss) during his first decade of life, and this is considered to be a notable finding. Our study also provides evidence emphasizing the need for genetic testing which could eliminate ambiguities in clinical diagnosis and detect carrier status, thereby aiding the patient and family members during genetic counseling.
PURPOSE:NDP-related retinopathies are a group of X-linked disorders characterized by degenerative and proliferative changes of the neuroretina, occasionally accompanied with varying degrees of mental retardation and sensorineural hearing loss. NDP is the predominant gene associated with NDP-related retinopathies. The purpose of this study was to report the clinical and genetic findings in three unrelated patients diagnosed with NDP-related retinopathies. METHODS: The patients underwent complete ophthalmic examination followed by genetic analyses. NDP gene was screened by direct sequencing approach. Targeted resequencing of several other ocular genes was carried out in patient samples that either indicated NDP gene deletion or tested negative for NDP mutation. Gene quantitation analysis was performed using real-time PCR. RESULTS: The whole NDP gene was deleted in patient I, while a missense NDP mutation, c.205T>C, was identified in patient II, and both had classical Norrie disease ocular phenotype (with no other systemic defects). Patient III who was diagnosed with familial exudative vitreoretinopathy did not show any mutation in the known candidate genes as well as in other ocular genes tested. CONCLUSIONS: The patient with whole NDP gene deletion did not exhibit any apparent extraocular defects (like mental retardation or sensorineural hearing loss) during his first decade of life, and this is considered to be a notable finding. Our study also provides evidence emphasizing the need for genetic testing which could eliminate ambiguities in clinical diagnosis and detect carrier status, thereby aiding the patient and family members during genetic counseling.
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