Mucopolysaccharidosis type IVA. N-acetylgalactosamine-6-sulfate sulfatase exonic point mutations in classical Morquio and mild cases.

Fukuda, Seiji; Tomatsu, Shunji; Masue, Michiya; Sukegawa, Kazuko; Iwata, Hisato; Ogawa, Tatsuya; Nakashima, Yoshihiro; Hori, Toshinori; Yamagishi, Atsushi; Hanyu, Yuko

doi:10.1172/jci115919

Cited by 59 publications

(38 citation statements)

References 20 publications

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“…Exonic single-nucleotide variations in GALNS may act in one or more of the following ways: (1) as a polymorphism that does not affect the gene's functions, (2) as a missense mutation resulting in reduced enzyme activities and (3) as a missense mutation that affects the formation of lysosomal multienzyme complex which is responsible for the stabilization of GALNS. 24,28,29 In vitro expression of mutant alleles has been used to judge the pathogenicity of missense mutations, 30 by assaying enzyme activities of plasmid containing mutant cDNA produced by site-direct mutagenesis. This method may be limited in distinguishing substitutions of residues involved in forming lysosomal multienzyme complex if they do not change enzyme activities greatly.…”

Section: Discussionmentioning

confidence: 99%

Mucopolysaccharidosis IVA mutations in Chinese patients: 16 novel mutations

et al. 2010

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Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is a lysosomal storage disease caused by deficiency of N-acetylgalactosamine-6-sulfatase (GALNS) and transmitted as an autosomal recessive trait. This is the first systematic mutation screen in Chinese MPS IVA patients. Mutation detections in 24 unrelated Chinese MPS IVA patients were performed by PCR and direct sequencing of exons or the mRNA of GALNS. A total of 42 mutant alleles were identified, belonging to 27 different mutations. Out of the 27 mutations, 16 were novel, including 2 splicing mutations (c.567-1G4T and c.634-1G4A),

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Section: Discussionmentioning

confidence: 99%

Mucopolysaccharidosis IVA mutations in Chinese patients: 16 novel mutations

et al. 2010

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“…Molecular analyses of MPS IVA patients were carried out in diverse ethnic origins, especially European and Japanese ancestries (Fukuda et al 1992;Tomatsu et al 1995;Ogawa et al 1995;Bunge et al 1997;Yamada et al 1998;Montano et al 2003). However, little has been reported on MPS IVA patients in the Latin American population.…”

Section: Introductionmentioning

confidence: 99%

Identification of a common mutation in mucopolysaccharidosis IVA: correlation among genotype, phenotype, and keratan sulfate

et al. 2004

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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 agematched 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.

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“…The GALNS enzyme activities in fibroblasts derived from both cases were 16-26% of normal controls (52). The genotypes of both cases are p.N204K/p.N204K (28). Case 4 died of myocardial infarction at the age of 52 years.…”

Section: B Musculoskeletal Observations Of Patients With Mucopolysacmentioning

confidence: 99%

“…More than 180 different mutations have been identified in the GALNS gene (7-10;25-28). Clinical presentations of severely affected patients have been reported as severe (29;30), or classical (28)(29)(30) phenotypes. Less severe forms of MPS IVA have been reported as mild (30;31) or attenuated (7;9) phenotypes.…”

Section: Introductionmentioning

confidence: 99%

A review of the clinical presentation and diagnosis of Mucopolysaccharidosis IVA

Tomatsu

Hendriksz

Harmatz³

et al. 2013

Molecular Genetics and Metabolism

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Mucopolysaccharidosis type IVA (MPS IVA) was described in 1929 by Luis Morquio from Uruguay and James Brailsford from England, and was later found as an autosomal recessive lysosomal storage disease. MPS IVA is caused by mutations in the gene encoding the enzyme, Nacetylgalactosamine-6-sulfate sulfatase (GALNS). Reduced GALNS activity results in impaired catabolism of two glycosaminoglycans (GAGs), chondroitin-6-sulfate (C6S) and keratan sulfate (KS). Clinical presentations of MPS IVA reflect a spectrum of progression from a severe "classical" phenotype to a mild "attenuated" phenotype. More than 180 different mutations have been identified in the GALNS gene, which likely explains the phenotypic heterogeneity of the disorder. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.All authors received reimbursement for participating in a BioMarin sponsored summit. The author contributions were presented in part at the summit and were not influenced by BioMarin. C.G. Gravance is an employee of BioMarin Pharmaceutical, Inc. NIH Public Access Author ManuscriptMol Genet Metab. Author manuscript; available in PMC 2014 September 01. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptAccumulation of C6S and KS manifests predominantly as short stature and skeletal dysplasia (dysostosis multiplex), including atlantoaxial instability and cervical cord compression. However, abnormalities in the visual, auditory, cardiovascular, and respiratory systems can also affect individuals with MPS IVA. Diagnosis is typically based on clinical examination, skeletal radiographs, urinary GAG, and enzymatic activity of GALNS in blood cells or fibroblasts. Deficiency of GALNS activity is a common assessment for the laboratory diagnosis of MPS IVA; however, with recently increased availability, gene sequencing for MPS IVA is often used to confirm enzyme results. As multiple clinical presentations are observed, diagnosis of MPS IVA may require multi-system considerations.This review provides a history of defining MPS IVA and how the understanding of the disease manifestations has changed over time. A summary of the accumulated knowledge is presented, including information from the International Morquio Registry. The classical phenotype is contrasted with attenuated cases, which are now being recognized and diagnosed more frequently. Laboratory based diagnoses of MPS IVA are also discussed.

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Mucopolysaccharidosis type IVA. N-acetylgalactosamine-6-sulfate sulfatase exonic point mutations in classical Morquio and mild cases.

Cited by 59 publications

References 20 publications

Mucopolysaccharidosis IVA mutations in Chinese patients: 16 novel mutations

Mucopolysaccharidosis IVA mutations in Chinese patients: 16 novel mutations

Identification of a common mutation in mucopolysaccharidosis IVA: correlation among genotype, phenotype, and keratan sulfate

A review of the clinical presentation and diagnosis of Mucopolysaccharidosis IVA

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