Identification of a common mutation in mucopolysaccharidosis IVA: Correlation among genotype, phenotype, and keratan sulfate
Journal
Journal of Human Genetics
ISSN
14345161
Date Issued
2004-10-14
Author(s)
Tomatsu, Shunji
Dieter, Tatiana
Schwartz, Ida V.
Sarmient, Piedad
Giugliani, Roberto
Barrera, Luis A.
Guelbert, Norberto
Kremer, Raquel
Gutierrez, Monica A.
Nishioka, Tatsuo
Peña Serrato, Olga
Montaño, Adriana Maria
Yamaguchi, Seiji
Noguchi, Akihiko
Type
Resource Types::text::journal::journal article
Abstract
Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disorder caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Mutation screening of the GALNS was performed by genomic PCR and direct sequence analyses in 20 MPS IVA patients from Latin America. In this study, 12 different gene mutations including nine unreported ones were identified in 16 severe and four attenuated patients and accounted for 90.0% of the unrelated mutant alleles. The gene alterations were missense mutations except one insertion. Six recurrent mutations, p.A75G, p.G116S, p.G139S, p.N164T, p.R380S, and p.R386C, accounted for 5.0, 10.0, 5.0, 7.5, 5.0, and 32.5% of the unrelated mutant alleles, respectively. The p.R386C mutation was identified in all Latin American populations studied. Eleven mutations correlated with a severe form, while one mutation, p.R380S, was associated with an attenuated form. MPS IVA patients had an elevation of urine and plasma keratan sulfate (KS) concentrations compared with those of the age-matched control. KS concentrations in severe patients were higher than those in attenuated patients. These data provide evidence for extensive allelic heterogeneity and presence of a common mutation in Latin American patients. Accumulation of mutations with clinical description and KS concentration will lead us to predict clinical severity of the patient more precisely.