title: Identification and characterization of 20 novel pathogenic variants in 60 unrelated Indian patients with mucopolysaccharidoses type I and type II.
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.
authors.affiliation: Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.|Graduate Studies, Manipal University, Manipal, India.
authors.forename: A
authors.initials: A
authors.lastname: Uttarilli
authors.affiliation: Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.|Department of Medical Genetics, Nizam's Institute of Medical Sciences, Hyderabad, India.
authors.forename: P
authors.initials: P
authors.lastname: Ranganath
authors.affiliation: Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
authors.forename: D
authors.initials: D
authors.lastname: Matta
authors.affiliation: Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
authors.forename: J
authors.initials: J
authors.lastname: Md Nurul Jain
authors.affiliation: Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
authors.forename: K
authors.initials: K
authors.lastname: Prasad
authors.affiliation: Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
authors.forename: A S
authors.initials: AS
authors.lastname: Babu
authors.affiliation: Department of Medical Genetics, Kasturba Medical College, Manipal, India.
authors.forename: K M
authors.identifier: 0000-0002-0139-8239
authors.initials: KM
authors.lastname: Girisha
authors.affiliation: Center of Medical Genetics, Sir Ganga Ram Hospital, New Delhi, India.
authors.forename: I C
authors.initials: IC
authors.lastname: Verma
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: S R
authors.initials: SR
authors.lastname: Phadke
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: K
authors.identifier: 0000-0003-2744-7825
authors.initials: K
authors.lastname: Mandal
authors.affiliation: Center of Medical Genetics, Sir Ganga Ram Hospital, New Delhi, India.
authors.forename: R D
authors.initials: RD
authors.lastname: Puri
authors.affiliation: Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.|Department of Medical Genetics, Nizam's Institute of Medical Sciences, Hyderabad, India.
authors.forename: S
authors.initials: S
authors.lastname: Aggarwal
authors.affiliation: Department of Clinical Genetics, Christian Medical College and Hospital, Vellore, India.
authors.forename: S
authors.initials: S
authors.lastname: Danda
authors.affiliation: Genetics Clinic, Department of Pediatrics, SAT Hospital, Government Medical College, Trivandrum, India.
authors.forename: V H
authors.initials: VH
authors.lastname: Sankar
authors.affiliation: Department of Pediatrics, Maulana Azad Medical College, New Delhi, India.
authors.forename: S
authors.initials: S
authors.lastname: Kapoor
authors.affiliation: Centre for Human Genetics, Bengaluru, India.
authors.forename: M
authors.initials: M
authors.lastname: Bhat
authors.affiliation: Kanchi Kamakoti CHILDS Trust Hospital, Chennai, India.
authors.forename: K
authors.initials: K
authors.lastname: Gowrishankar
authors.affiliation: Department of Genetics, Kamineni Hospital, Hyderabad, India.
authors.forename: A Q
authors.initials: AQ
authors.lastname: Hasan
authors.affiliation: Additional Professor in Pediatrics, Government Medical College, Manjeri, India.
authors.forename: M
authors.initials: M
authors.lastname: Nair
authors.affiliation: Department of Pediatric Genetics, Amrita Institute of Medical Sciences, Kochi, India.
authors.forename: S
authors.initials: S
authors.lastname: Nampoothiri
authors.affiliation: Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
authors.forename: A
authors.initials: A
authors.lastname: Dalal
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007068:Iduronidase / Q000737:chemistry / Q000235:genetics*; D007194:India; D007223:Infant; D008297:Male; D008059:Mucopolysaccharidosis I / Q000235:genetics* / Q000503:physiopathology; D016532:Mucopolysaccharidosis II / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011487:Protein Conformation; D017384:Sequence Deletion / Q000235:genetics; D013329:Structure-Activity Relationship
chemical_list: D006023:Glycoproteins; C018322:IDS protein, human; C000615655:IDUA protein, human; D007068:Iduronidase
keywords: Hunter syndrome; Hurler syndrome; genotype-phenotype correlation; mucopolysaccharidoses; mucopolysaccharidosis type I; mucopolysaccharidosis type II; variant