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Divya, Pasumarthi and Gupta, N. and Sheth, J. and Jain, J.M.N. and Rungsung, I. and Kabra, M. and Ranganath, Prajnya and Aggarwal, Shagun and Phadke, S.R. and Girisha, K.M. and Shukla, A. and Datar, C. and Verma, I.C. and Puri, R.D. and Bhavsar, R. and Mistry, M. and Sankar, V.H. and Gowrishankar, K. and Agrawal, Divya and Nair, M. and Danda, S. and Soni, J.P. and Dalal, Ashwin (2020) Identification and characterization of 30 novel pathogenic variations in 69 unrelated Indian patients with Mucolipidosis Type II and Type III. Journal of Human Genetics, 65 (11). pp. 971-984. ISSN 1434-5161

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Mucolipidosis (ML) (OMIM 607840 & 607838) is a rare autosomal recessive inherited disorder that occurs due to the deficiency of golgi enzyme uridine diphosphate (UDP)- N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase) responsible for tagging mannose-6-phosphate for proper trafficking of lysosomal enzymes to lysosomes. Variants in GlcNAc-phosphotransferase (GNPTAB (α, β subunits) and GNPTG (γ subunits) are known to result in impaired targeting of lysosomal enzymes leading to Mucolipidosis (ML) Type II or Type III. We analyzed 69 Indian families of MLII/III for clinical features and molecular spectrum and performed in silico analysis for novel variants. We identified 38 pathogenic variants in GNPTAB and 5 pathogenic variants in GNPTG genes including missense, frame shift, deletion, duplication and splice site variations. A total of 26 novel variants were identified in GNPTAB and 4 in GNPTG gene. In silico studies using mutation prediction software like SIFT, Polyphen2 and protein structure analysis further confirmed the pathogenic nature of the novel sequence variants detected in our study. Except for a common variant c.3503_3504delTC in early onset MLII, we could not establish any other significant genotype and phenotype correlation. This is one of the largest studies reported till date on Mucolipidosis II/III in order to identify mutation spectrum and any recurrent mutations specific to the Indian ethnic population. The mutational spectrum information in Indian patients will be useful in better genetic counselling, carrier detection and prenatal diagnosis for patients with ML II/III.

Item Type: Article
Subjects: Genetics
Depositing User: Dr P. Divakar
Date Deposited: 13 Jul 2020 19:40
Last Modified: 10 Nov 2020 19:08
URI: http://cdfd.sciencecentral.in/id/eprint/959

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