Identification and characterization of 20 novel pathogenic variants in 60 unrelated Indian patients with mucopolysaccharidoses type I and type II

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 & 1 others A. Dalal

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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.

Original languageEnglish
Pages (from-to)496-508
Number of pages13
JournalClinical Genetics
Volume90
Issue number6
DOIs
Publication statusPublished - 01-12-2016

Fingerprint

Mucopolysaccharidosis II
Mucopolysaccharidosis I
Iduronidase
Mucopolysaccharidoses
Mutation
Iduronate Sulfatase
Population
Glycosaminoglycans
Computer Simulation

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Uttarilli, A. ; Ranganath, P. ; Matta, D. ; Md Nurul Jain, J. ; Prasad, K. ; Babu, A. S. ; Girisha, K. M. ; Verma, I. C. ; Phadke, S. R. ; Mandal, K. ; Puri, R. D. ; Aggarwal, S. ; Danda, S. ; Sankar, V. H. ; Kapoor, S. ; Bhat, M. ; Gowrishankar, K. ; Hasan, A. Q. ; Nair, M. ; Nampoothiri, S. ; Dalal, A. / Identification and characterization of 20 novel pathogenic variants in 60 unrelated Indian patients with mucopolysaccharidoses type I and type II. In: Clinical Genetics. 2016 ; Vol. 90, No. 6. pp. 496-508.
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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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Uttarilli, A, Ranganath, P, Matta, D, Md Nurul Jain, J, Prasad, K, Babu, AS, Girisha, KM, Verma, IC, Phadke, SR, Mandal, K, Puri, RD, Aggarwal, S, Danda, S, Sankar, VH, Kapoor, S, Bhat, M, Gowrishankar, K, Hasan, AQ, Nair, M, Nampoothiri, S & Dalal, A 2016, 'Identification and characterization of 20 novel pathogenic variants in 60 unrelated Indian patients with mucopolysaccharidoses type I and type II', Clinical Genetics, vol. 90, no. 6, pp. 496-508. https://doi.org/10.1111/cge.12795

Identification and characterization of 20 novel pathogenic variants in 60 unrelated Indian patients with mucopolysaccharidoses type I and type II. / Uttarilli, A.; Ranganath, P.; Matta, D.; Md Nurul Jain, J.; Prasad, K.; Babu, A. S.; Girisha, K. M.; Verma, I. C.; Phadke, S. R.; Mandal, K.; Puri, R. D.; Aggarwal, S.; Danda, S.; Sankar, V. H.; Kapoor, S.; Bhat, M.; Gowrishankar, K.; Hasan, A. Q.; Nair, M.; Nampoothiri, S.; Dalal, A.

In: Clinical Genetics, Vol. 90, No. 6, 01.12.2016, p. 496-508.

Research output: Contribution to journalArticle

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T1 - Identification and characterization of 20 novel pathogenic variants in 60 unrelated Indian patients with mucopolysaccharidoses type I and type II

AU - Uttarilli, A.

AU - Ranganath, P.

AU - Matta, D.

AU - Md Nurul Jain, J.

AU - Prasad, K.

AU - Babu, A. S.

AU - Girisha, K. M.

AU - Verma, I. C.

AU - Phadke, S. R.

AU - Mandal, K.

AU - Puri, R. D.

AU - Aggarwal, S.

AU - Danda, S.

AU - Sankar, V. H.

AU - Kapoor, S.

AU - Bhat, M.

AU - Gowrishankar, K.

AU - Hasan, A. Q.

AU - Nair, M.

AU - Nampoothiri, S.

AU - Dalal, A.

PY - 2016/12/1

Y1 - 2016/12/1

N2 - 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.

AB - 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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