Identification of a novel missense mutation in Brazilian patient with a severe form of mucopolysaccharidosis type IVA

Gene. 2013 Mar 15;517(1):112-5. doi: 10.1016/j.gene.2012.12.100. Epub 2013 Jan 11.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Amino Acid Sequence
  • Brazil
  • Chondroitinsulfatases / genetics*
  • Enzyme Replacement Therapy
  • Female
  • Genetic Association Studies
  • Humans
  • Molecular Sequence Data
  • Mucopolysaccharidosis IV / diagnosis
  • Mucopolysaccharidosis IV / genetics*
  • Mucopolysaccharidosis IV / therapy
  • Mutation, Missense / genetics*
  • Prognosis
  • Sequence Homology, Amino Acid

Substances

  • Chondroitinsulfatases
  • GALNS protein, human