title: Genotypic and bioinformatic evaluation of the alpha-l-iduronidase gene and protein in patients with mucopolysaccharidosis type I from Colombia, Ecuador and Peru.
abstract: Mucopolysaccharidosis type I (MPSI) is a rare autosomal recessive disorder caused by mutations in the gene encoding the lysosomal enzyme α-l-iduronidase (IDUA), which is instrumental in the hydrolysis of the glycosaminoglycans, dermatan and heparan sulfate. The accumulation of unhydrolyzed glycosaminoglycans leads to pathogenesis in multiple tissue types, especially those of skeletal, nervous, respiratory, cardiovascular, and gastrointestinal origin. Although molecular diagnostic tools for MPSI have been available since the identification and characterization of the IDUA gene in 1992, Colombia, Ecuador, and Peru have lacked such methodologies. Therefore, the mutational profile of the IDUA gene in these countries has largely been unknown. The goal of this study was to characterize genotypes in 14 patients with MPSI from Colombia, Ecuador, and Peru. The most common mutation found at a frequency of 42.8% was W402X. Six patients presented with seven novel mutations, a high novel mutational rate in this population (32%). These novel mutations were validated using bioinformatic techniques. A model of the IDUA protein resulting from three of the novel missense mutations (Y625C, P385L, R621L) revealed that these mutations alter accessible surface area values, thereby reducing the accessibility of the enzyme to its substrates. This is the first characterization of the mutational profile of the IDUA gene in patients with MPSI in Colombia, Ecuador, and Peru. The findings contribute to our understanding of IDUA gene expression and IDUA enzyme function, and may help facilitate early and improved diagnosis and management for patients with MPSI.
authors.affiliation: Genetics Institute, Faculty of Medicine, National University of Colombia, Bogotá DC, Colombia.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Pineda
authors.affiliation: Faculty of Medicine, São Paulo University, São Paulo, Brazil.
authors.forename: Sulie
authors.initials: S
authors.lastname: Marie
authors.affiliation: Nutrition Department, Faculty of Sciences, Javeriana University, Bogotá, DC, Colombia.
authors.forename: Janneth
authors.initials: J
authors.lastname: Gonzalez
authors.affiliation: Pediatrics Neurology Department, Simon Bolívar Hospital, Bogotá, DC, Colombia.
authors.forename: Ana L
authors.initials: AL
authors.lastname: García
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Cauca University, Popayán, Colombia.
authors.forename: Amparo
authors.initials: A
authors.lastname: Acosta
authors.affiliation: Pediatrics Neurology Department, Children Colsubsidio Hospital, Bogotá, DC, Colombia.
authors.forename: Manuel
authors.initials: M
authors.lastname: Morales
authors.affiliation: Pediatrics Neurology Department, La Misericordia Hospital, Bogotá, DC, Colombia.
authors.forename: Luz N
authors.initials: LN
authors.lastname: Correa
authors.affiliation: Pediatrics Neurology Department, Sogamoso Regional Hospital, Sogamoso, Colombia.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Vivas
authors.affiliation: Pediatrics Neurology Department, San Jeronico Regional Hospital of Montería, Monteria, Colombia.
authors.forename: Xiomara
authors.initials: X
authors.lastname: Escobar
authors.affiliation: Genetics Department, National E Rebagliati Martins Hospital, Lima, Peru.
authors.forename: Ana
authors.initials: A
authors.lastname: Protzel
authors.affiliation: Cordero E 9-39 y 6 de Diciembre, Edificio San Francisco, Consultorio, 31, Quito, Ecuador.
authors.forename: Maria
authors.initials: M
authors.lastname: Barba
authors.affiliation: Clinica Salud Coop, Bogotá, Colombia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Ospina
authors.affiliation: Pediatrics Department, Duitama Regional Hospital, Duitama, Colombia.
authors.forename: Clara
authors.initials: C
authors.lastname: Corredor
authors.affiliation: Pediatrics Neurology Department, Federico Lleras Hospital, Ibagué, Colombia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Mansilla
authors.affiliation: Genetics Institute, Faculty of Medicine, National University of Colombia, Bogotá DC, Colombia.
authors.forename: Harvy M
authors.initials: HM
authors.lastname: Velasco
keywords: Bioinformatic model; Hurler; Mucopolysaccharidosis type I; Mutational analysis; Scheie; α-l-Iduronidase