title: Identification of a novel missense mutation in Brazilian patient with a severe form of mucopolysaccharidosis type IVA.
abstract: Mucopolysaccharidosis type IVA (MPS IVA) or Morquio syndrome type A is an autosomal recessive disease caused by deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfatase (GALNS). We report molecular characterization of a patient who presents the new missense mutation p.C165Y in homozygosis. Bioinformatics analysis predicted this mutation as being probably pathogenic. To evaluate the possibility that this alteration was a polymorphism we tested 100 alleles and all the results were negative. These findings together with the observation that this alteration is not present in controls, suggest that it is a disease-causing mutation, which was correlated with the severe phenotype observed in our patient. We conclude that molecular analysis of the GALNS gene, in addition to enzyme assays, is important for diagnosis and contributes to the better understanding of the relationship between genotype and phenotype, which is important as enzyme replacement therapy (ERT) will soon become available and treatment decisions will have to be take in such cases.
authors: Post Graduation Program in Medicine: Medical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors: Francyne
authors: F
authors: Kubaski
authors: Ana Carolina
authors: AC
authors: Brusius-Facchin
authors: Heloísa M C
authors: HM
authors: Palhares
authors: Marly Aparecida Spadotto
authors: MA
authors: Balarin
authors: Marli
authors: M
authors: Viapiana-Camelier
authors: Regis
authors: R
authors: Guidobono
authors: Maira Graeff
authors: MG
authors: Burin
authors: Roberto
authors: R
authors: Giugliani
authors: Sandra
authors: S
authors: Leistner-Segal
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D001938:Brazil; D002811:Chondroitinsulfatases / Q000235:genetics*; D056947:Enzyme Replacement Therapy; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008969:Molecular Sequence Data; D009085:Mucopolysaccharidosis IV / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D020125:Mutation, Missense / Q000235:genetics*; D011379:Prognosis; D017386:Sequence Homology, Amino Acid
chemical_list: D002811:Chondroitinsulfatases; C102295:GALNS protein, human