Molecular analysis of mucopolysaccharidosis IVA (Morquio A) in Spain
Por:
Pajares S, Alcalde C, Couce ML, Del Toro M, González-Meneses A, Guillén 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.
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