Identification and characterization of 20 novel pathogenic variants in 60 unrelated Indian patients with mucopolysaccharidoses type I and type II |
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| Authors: | A. Uttarilli P. Ranganath D. Matta J. Md Nurul Jain K. Prasad A.S. Babu K.M. Girisha I.C. Verma S.R. Phadke K. Mandal R.D. Puri S. Aggarwal S. Danda V.H. Sankar S. Kapoor M. Bhat K. Gowrishankar A.Q. Hasan M. Nair S. Nampoothiri A. Dalal |
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| Affiliation: | 1. Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India;2. Graduate Studies, Manipal University, Manipal, India;3. Department of Medical Genetics, Nizam's Institute of Medical Sciences, Hyderabad, India;4. Department of Medical Genetics, Kasturba Medical College, Manipal, India;5. Center of Medical Genetics, Sir Ganga Ram Hospital, New Delhi, India;6. Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India;7. Department of Clinical Genetics, Christian Medical College and Hospital, Vellore, India;8. Genetics Clinic, Department of Pediatrics, SAT Hospital, Government Medical College, Trivandrum, India;9. Department of Pediatrics, Maulana Azad Medical College, New Delhi, India;10. Centre for Human Genetics, Bengaluru, India;11. Kanchi Kamakoti CHILDS Trust Hospital, Chennai, India;12. Department of Genetics, Kamineni Hospital, Hyderabad, India;13. Additional Professor in Pediatrics, Government Medical College, Manjeri, India;14. Department of Pediatric Genetics, Amrita Institute of Medical Sciences, Kochi, India |
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| Abstract: | Mucopolysaccharidoses (MPS), a subgroup of lysosomal storage disorders, are caused due to deficiency of specific lysosomal enzyme involved in catabolism of glycosaminoglycans. To date more than 200 pathogenic variants in the alpha‐l ‐iduronidase (IDUA) for MPS I and ～500 pathogenic variants in the iduronate‐2‐sulphatase (IDS) for MPS II have been reported worldwide. The mutation spectrum of MPS type I and MPS type II disorders in Indian population is not characterized yet. In this study, we carried out clinical, biochemical, molecular and in silico analyses to establish the mutation spectrum of MPS I and MPS II in the Indian population. We conducted molecular analysis for 60 MPS‐affected patients [MPS I (n = 30) (Hurler syndrome = 17, Hurler–Scheie syndrome = 13), and MPS II (n = 30) (severe = 18, attenuated = 12)] and identified a total of 44 [MPS I (n = 22) and MPS II (n = 22)] different pathogenic variants comprising missense, nonsense, frameshift, gross deletions and splice site variants. A total of 20 [MPS I (n = 14), and MPS II (n = 6)] novel pathogenic sequence variants were identified in our patient cohort. We found that 32% of pathogenic variants detected in IDUA were recurrent and 25% in MPS II. This is the first study revealing the mutation spectrum of MPS I and MPS II patients in the Indian population. |
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| Keywords: | genotype– phenotype correlation Hunter syndrome Hurler syndrome mucopolysaccharidoses mucopolysaccharidosis type I mucopolysaccharidosis type II variant |
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