Identification of a novel missense mutation in Brazilian patient with a severe form of mucopolysaccharidosis type IVA |
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Authors: | Francyne Kubaski,Ana Carolina Brusius-Facchin,Heloí sa M.C. Palhares,Marly Aparecida Spadotto Balarin,Marli Viapiana-Camelier,Regis Guidobono,Maira Graeff Burin,Roberto Giugliani,Sandra Leistner-Segal |
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Affiliation: | 1. Post Graduation Program in Medicine: Medical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil;2. Medical Genetics Service, Hospital de Clinicas de Porto Alegre, RS, Brazil;3. Endocrinology and Genetics Services, Federal University of Triângulo Mineiro (UFTM), MG, Brazil;4. Biological and Natural Sciences Institute (ICBN), Federal University of Triângulo Mineiro (UFTM), MG, Brazil;5. Department of Genetics, UFRGS, RS, Brazil |
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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. |
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Keywords: | AAS, amino acid substitution ARSA, arylsulfatase A or heparan-N-sulfatase ARSB, arylsulfatase B or N-acetylgalactosamine-4-sulfatase ARSC, arylsulfatase C or acetyl-CoA:alpha-glucosaminide acetyltransferase C, cysteine ° C, degrees Celsius cDNA, DNA complementary to RNA C6S, chondroitin-6-sulfate cm, centimeters ERT, enzyme replacement therapy GAGs, glycosaminoglycans GALNS, N-acetylgalactosamine-6-sulfatase G6S, N-acetyl-glucosamine-6-sulfate sulfatase H, histidine h, hours IDS, iduronate-2-sulfatase kb, kilobase(s) or 1000 bp Kg, kilograms KS, keratan sulfate MPS IVA, mucopolysaccharidosis type IVA MDE, mutation detection electrophoresis gel solution min, minutes ml, milliliters N, asparagine pmol, picomoles Q, glutamine RFLP, restriction-fragment length polymorphism SSCP, single-strand conformation polymorphism T, threonine V, volts Y, tyrosine μl, microliters |
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