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A novel p.E276K IDUA mutation decreasing α-L-iduronidase activity causes mucopolysaccharidosis type I

PURPOSE: To characterize the pathogenic mutations causing mucopolysaccharidosis type I (MPS I) in two Thai patients: one with Hurler syndrome (MPS IH), the most severe form, and the other with Scheie syndrome (MPS IS), the mildest. Both presented with distinctive phenotype including corneal clouding...

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Autores principales: Prommajan, Korrakot, Ausavarat, Surasawadee, Srichomthong, Chalurmpon, Puangsricharern, Vilavun, Suphapeetiporn, Kanya, Shotelersuk, Vorasuk
Formato: Texto
Lenguaje:English
Publicado: Molecular Vision 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3042362/
https://www.ncbi.nlm.nih.gov/pubmed/21364962
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author Prommajan, Korrakot
Ausavarat, Surasawadee
Srichomthong, Chalurmpon
Puangsricharern, Vilavun
Suphapeetiporn, Kanya
Shotelersuk, Vorasuk
author_facet Prommajan, Korrakot
Ausavarat, Surasawadee
Srichomthong, Chalurmpon
Puangsricharern, Vilavun
Suphapeetiporn, Kanya
Shotelersuk, Vorasuk
author_sort Prommajan, Korrakot
collection PubMed
description PURPOSE: To characterize the pathogenic mutations causing mucopolysaccharidosis type I (MPS I) in two Thai patients: one with Hurler syndrome (MPS IH), the most severe form, and the other with Scheie syndrome (MPS IS), the mildest. Both presented with distinctive phenotype including corneal clouding. METHODS: The entire coding regions of the α-L-iduronidase (IDUA) gene were amplified by PCR and sequenced. Functional characterization of the mutant IDUA was determined by transient transfection of the construct into COS-7 cells. RESULTS: Mutation analyses revealed that the MPS IH patient was homozygous for a previously reported mutation, c.252insC, while the MPS IS patient was found to harbor a novel c.826G>A (p.E276K) mutation. The novel p.E276K mutation was not detected in 100 unaffected ethnic-matched control chromosomes. In addition, the glutamic acid residue at codon 276 was located at a well conserved residue. Transient transfection of the p.E276K construct revealed a significant reduction of IDUA activity compared to that of the wild-type IDUA suggesting it as a disease-causing mutation. CONCLUSIONS: This study reports a novel mutation, expanding the mutational spectrum for MPS I.
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spelling pubmed-30423622011-03-01 A novel p.E276K IDUA mutation decreasing α-L-iduronidase activity causes mucopolysaccharidosis type I Prommajan, Korrakot Ausavarat, Surasawadee Srichomthong, Chalurmpon Puangsricharern, Vilavun Suphapeetiporn, Kanya Shotelersuk, Vorasuk Mol Vis Research Article PURPOSE: To characterize the pathogenic mutations causing mucopolysaccharidosis type I (MPS I) in two Thai patients: one with Hurler syndrome (MPS IH), the most severe form, and the other with Scheie syndrome (MPS IS), the mildest. Both presented with distinctive phenotype including corneal clouding. METHODS: The entire coding regions of the α-L-iduronidase (IDUA) gene were amplified by PCR and sequenced. Functional characterization of the mutant IDUA was determined by transient transfection of the construct into COS-7 cells. RESULTS: Mutation analyses revealed that the MPS IH patient was homozygous for a previously reported mutation, c.252insC, while the MPS IS patient was found to harbor a novel c.826G>A (p.E276K) mutation. The novel p.E276K mutation was not detected in 100 unaffected ethnic-matched control chromosomes. In addition, the glutamic acid residue at codon 276 was located at a well conserved residue. Transient transfection of the p.E276K construct revealed a significant reduction of IDUA activity compared to that of the wild-type IDUA suggesting it as a disease-causing mutation. CONCLUSIONS: This study reports a novel mutation, expanding the mutational spectrum for MPS I. Molecular Vision 2011-02-11 /pmc/articles/PMC3042362/ /pubmed/21364962 Text en Copyright © 2011 Molecular Vision. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Prommajan, Korrakot
Ausavarat, Surasawadee
Srichomthong, Chalurmpon
Puangsricharern, Vilavun
Suphapeetiporn, Kanya
Shotelersuk, Vorasuk
A novel p.E276K IDUA mutation decreasing α-L-iduronidase activity causes mucopolysaccharidosis type I
title A novel p.E276K IDUA mutation decreasing α-L-iduronidase activity causes mucopolysaccharidosis type I
title_full A novel p.E276K IDUA mutation decreasing α-L-iduronidase activity causes mucopolysaccharidosis type I
title_fullStr A novel p.E276K IDUA mutation decreasing α-L-iduronidase activity causes mucopolysaccharidosis type I
title_full_unstemmed A novel p.E276K IDUA mutation decreasing α-L-iduronidase activity causes mucopolysaccharidosis type I
title_short A novel p.E276K IDUA mutation decreasing α-L-iduronidase activity causes mucopolysaccharidosis type I
title_sort novel p.e276k idua mutation decreasing α-l-iduronidase activity causes mucopolysaccharidosis type i
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3042362/
https://www.ncbi.nlm.nih.gov/pubmed/21364962
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