Molecular analysis of mucopolysaccharidosis IVA (Morquio A) in Spain
Por:
Pajares, S, Alcalde, C, Couce, ML, Del Toro, M, Gonzalez-Meneses, A, Guillen, E, Pineda, M, Pintos, G, Gort, L and Coll, MJ
Publicada:
1 jun 2012
Resumen:
Mucopolysaccharidosis type IVA (Morquio A) is an inherited metabolic disease with autosomal recessive inheritance. The pathology is due to a deficient activity of N-acetylgalactosamine-6-sulfate-sulfatase, which is involved in the degradation of keratan sulfate and chondroitin-6-sulfate. To date more than 150 mutations have been described in the GALNS gene in different populations. The aim of this study was to analyze the mutations and polymorphisms in Spain in order to know the epidemiology of our population and also to offer genetic counseling to affected families.
We found 30 mutant alleles in the 15 families analyzed completing all the genotypes. Most of the mutations that we found were missense mutations, six of which were novel: p.S74F, p.E121D, p.Y254C, p.E260K, p.T394P and p.N495Y; we also found a small deletion (c.1142delC) and a probable deep intronic mutation that causes the loss of exon 5 (c.423_566del) found in cDNA. Both mutations are described in this study for the first time. We also identified 20 polymorphisms previously reported and 2 novel ones: (c.633 + 222 T/C and c.898 + 25 C>G).
In conclusion, we have identified the mutations responsible for Mucopolysaccharidosis IV A in Spain. We found great allelic heterogeneity, as occurs in other populations, which hinders the establishment of genotype-phenotype correlations in Spain. This study has been very useful for genetic counseling to the affected families. (C) 2012 Published by Elsevier Inc.
Filiaciones:
Pajares, S:
Hosp Clin Barcelona, Secc Errores Congenitos Metab IBC, Serv Bioquim & Genet Mol, CIBERER,IDIBAPS, Barcelona 080028, Spain
Alcalde, C:
Hosp Univ Rio Hortega, Serv Pediat, Valladolid, Spain
Couce, ML:
Hosp Gen Santiago de Compostela, Serv Neuropediat, Santiago De Compostela, Spain
Del Toro, M:
Hosp Univ Vall de Hebron, Serv Pediat, Barcelona, Spain
Gonzalez-Meneses, A:
Hosp Univ Virgen del Rocio, Unidad Dismorfol, Seville, Spain
Guillen, E:
Hosp Univ Virgen de la Arrixaca, Serv Pediat, Unidad Genet Med, Murcia, Spain
Pineda, M:
Hosp St Joan de Deu, Serv Pediat, Barcelona, Spain
:
Hosp Badalona Germans Trias & Pujol, Serv Pediat, Badalona, Spain
Gort, L:
Hosp Clin Barcelona, Secc Errores Congenitos Metab IBC, Serv Bioquim & Genet Mol, CIBERER,IDIBAPS, Barcelona 080028, Spain
Coll, MJ:
Hosp Clin Barcelona, Secc Errores Congenitos Metab IBC, Serv Bioquim & Genet Mol, CIBERER,IDIBAPS, Barcelona 080028, Spain
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