Novel mutations of the arylsulphatase B (ARSB) gene in Indian patients with mucopolysaccharidosis type VI.

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dc.contributor.authorUttarilli, Anusha
dc.contributor.authorRanganath, Prajnya
dc.contributor.authorJain, S Jamal Md Nurul
dc.contributor.authorPrasad, C Krishna
dc.contributor.authorSinha, Anupam
dc.contributor.authorVerma, Ishwar C
dc.contributor.authorPhadke, Shubha R
dc.contributor.authorPuri, Ratna D
dc.contributor.authorDanda, Sumita
dc.contributor.authorMuranjan, Mamta N
dc.contributor.authorJevalikar, Ganesh
dc.contributor.authorNagarajaram, H A
dc.contributor.authorDalal, Ashwin B
dc.date.accessioned2016-01-12T06:05:25Z
dc.date.available2016-01-12T06:05:25Z
dc.date.issued2015-10
dc.description.abstractBackground & objectives: Mucopolysaccharidosis type VI (MPS VI) is a rare, autosomal recessive lysosomal storage disorder caused by deficient enzymatic activity of N-acetyl galactosamine-4-sulphatase resulting from mutations in the arylsulphatase B (ARSB) gene. The ARSB gene is located on chromosome 5q11-q13 and is composed of eight exons. More than hundred ARSB mutations have been reported so far, but the mutation spectrum of MPS VI in India is still unknown. Hence, the aim of the present study was to identify the mutational spectrum in patients with MPS VI in India and to study the genotype-phenotype association and functional outcomes of these mutations. Methods: Molecular characterization of the ARSB gene by Sanger sequencing was done for 15 patients (aged 15 months to 11 yr) who were enzymatically confirmed to have MPS VI. Age of onset, clinical progression and enzyme activity levels in each patient were studied to look for genotype-phenotype association. Haplotype analysis performed for unrelated patients with the recurring mutation W450C, was suggestive of a founder effect. Sequence and structural analyses of the ARSB protein using standard software were carried out to determine the impact of detected mutations on the function of the ARSB protein. Results: A total of 12 mutations were identified, of which nine were novel mutations namely, p.D53N, p.L98R, p.Y103SfsX9, p.W353X, p.H393R, p.F166fsX18, p.I220fsX5, p.W450L, and p.W450C, and three were known mutations (p.D54N, p.A237D and p.S320R). The nine novel sequence variants were confirmed not to be polymorphic variants by performing sequencing in 50 unaffected individuals from the same ethnic population. Interpretation & conclusions: Nine novel mutations were identified in MPS VI cases from India in the present study. The study also provides some insights into the genotype-phenotype association in MPS VI.en_US
dc.identifier.citationUttarilli Anusha, Ranganath Prajnya, Jain S Jamal Md Nurul, Prasad C Krishna, Sinha Anupam, Verma Ishwar C, Phadke Shubha R, Puri Ratna D, Danda Sumita, Muranjan Mamta N, Jevalikar Ganesh, Nagarajaram H A, Dalal Ashwin B. Novel mutations of the arylsulphatase B (ARSB) gene in Indian patients with mucopolysaccharidosis type VI. Indian Journal of Medical Research. 2015 Oct; 142(4): 414-425.en_US
dc.identifier.urihttps://imsear.searo.who.int/handle/123456789/170335
dc.language.isoenen_US
dc.source.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4683826/en_US
dc.subjectARSB geneen_US
dc.subjectARSB protein structural analysisen_US
dc.subjectgenotype-phenotype associationen_US
dc.subjectIndian patientsen_US
dc.subjectmucopolysaccharidosis type VIen_US
dc.subjectmutationsen_US
dc.titleNovel mutations of the arylsulphatase B (ARSB) gene in Indian patients with mucopolysaccharidosis type VI.en_US
dc.typeArticleen_US
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