title: Genetic Screening of Mutations Associated with Fabry Disease in a Nationwide Cohort of Juvenile Idiopathic Arthritis Patients.
abstract: Fabry's disease (FD) is a lysosomal storage disorder associated with an alpha-galactosidase A deficiency. The prevalence of FD among juvenile idiopathic arthritis (JIA) patients with established diagnosis is unknown, but as musculoskeletal pain may be an important complaint at presentation, misdiagnosed cases are anticipated. With this study, we aim to calculate the frequency of FD-associated mutations in a cohort of JIA patients. Children with JIA from a national cohort were selected. Clinical and laboratorial information was recorded in the Portuguese rheumatic diseases register (http://Reuma.pt). Molecular genetic testing to detectGLAgene mutations was performed. After the multiplex polymerase chain reactions technique for DNA amplification, direct sequencing of the complete sequence ofGLAgene was completed. From a cohort of 292 patients with JIA (188 females, 104 males), mutations were identified in 5 patients (all female). Four patients had the mutation D313Y, a rareGLAvariant, which is associated with low enzymatic levels in plasma, but normal lysosomal levels. One patient presented the missense mutation R118C, which was previously described in Mediterranean patients with FD. This is the first screening of FD mutations in a cohort of JIA patients. No "classic" pathogenic FD mutations were reported. The late-onset FD-associated mutation, R118C, was found in a frequency of 0.34% (1/292).
authors.affiliation: Rheumatology Department, Hospital Santa Maria, Lisbon Academic Medical Centre, Lisboa, Portugal; Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Gonçalves
authors.affiliation: Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal; Rheumatology Department, Centro Hospitalar de Lisboa Ocidental, Lisboa, Portugal.
authors.forename: Ana F
authors.initials: AF
authors.lastname: Mourão
authors.affiliation: Centro de Histocompatibilidade do Centro , Coimbra , Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Martinho
authors.affiliation: Centro de Histocompatibilidade do Centro , Coimbra , Portugal.
authors.forename: Olívia
authors.initials: O
authors.lastname: Simões
authors.affiliation: Instituto Português de Reumatologia , Lisboa , Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Melo-Gomes
authors.affiliation: Pediatric Rheumatology Unit, Hospital Pediátrico de Coimbra , Coimbra , Portugal.
authors.forename: Manuel
authors.initials: M
authors.lastname: Salgado
authors.affiliation: Pediatric Rheumatology Unit, Hospital Pediátrico de Coimbra , Coimbra , Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Estanqueiro
authors.affiliation: Rheumatology Department, Hospital de Faro , Faro , Portugal.
authors.forename: Célia
authors.initials: C
authors.lastname: Ribeiro
authors.affiliation: Rheumatology Department, Centro Hospitalar S. João , Porto , Portugal.
authors.forename: Iva
authors.initials: I
authors.lastname: Brito
authors.affiliation: Rheumatology Department, Hospital Santa Maria, Lisbon Academic Medical Centre, Lisboa, Portugal; Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal.
authors.forename: João E
authors.initials: JE
authors.lastname: Fonseca
authors.affiliation: EpiDoC, CEDOC, Nova Medical School , Lisbon , Portugal.
authors.forename: Helena
authors.initials: H
authors.lastname: Canhão
keywords: Fabry disease; cohort; juvenile idiopathic arthritis; pain; register