Molecular testing of 163 patients with Morquio A (Mucopolysaccharidosis IVA) identifies 39 novel GALNS mutations

• Type of Material: Article
• Authors: A Morrone, Meyer Children's Hospital; K. L. Tylee, Central Manchester University Hospitals; M Al-Sayed, King Faisal Specialist Hospital and Research Center; A. C. Brusius-Facchin, Hospital de Clínicas de Porto Alegre; A. Caciotti, Meyer Children's Hospital; H. J. Church, Central Manchester University Hospitals; M. J. Coll, Hospital Clínic Barcelona; K. Davidson, BioMarin Pharmaceutical Inc.; M. J. Fietz, Women's and Children's Hospital; L. Gort, Hospital Clínic Barcelona; Madhuri Hegde, Emory University; F. Kubaski, Hospital de Clínicas de Porto Alegre; L. Lacerda, Centro Hospitalar do Porto; F. Laranjeira, Centro Hospitalar do Porto; S. Leistner-Segal, Hospital de Clínicas de Porto Alegre; S. Mooney, Buck Institute for Research on Aging; S. Pajares, Hospital Clínic Barcelona; L. Pollard, Greenwood Genetic Center; I. Ribeiro, Centro Hospitalar do Porto; R. Y. Wang, Children's Hospital of Orange County; N. Miller, BioMarin Pharmaceutical Inc.
• Language: English
• Date: 2014-06-01
• Publisher: Elsevier: 12 months
• Publication Version: Final Published Version
• Copyright Statement: © 2014 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ymgme.2014.03.004
• Title of Journal or Parent Work: Molecular Genetics and Metabolism
• ISSN: 1096-7192
• Volume: 112
• Issue: 2
• Start Page: 160
• End Page: 170
• Grant/Funding Information: Medical writing support was provided by Dr Karl Zawadzki and Dr Sue Currie of Health Interactions; with funding provided by BioMarin Pharmaceutical Inc.
• Keywords: N-ACETYLGALACTOSAMINE-6-SULFATE SULFATASE; LARGE DELETION; TANDEM MASS-SPECTROMETRY; Life Sciences & Biomedicine; LYSOSOMAL STORAGE DISORDERS; Endocrinology & Metabolism; GALNS; KERATAN SULFATE; NORTHERN-IRELAND; APPARENT HOMOZYGOSITY; Mutation; MISSENSE MUTATIONS; Medicine, Research & Experimental; Mucopolysaccharidosis type IVA; Lysosomal storage disorder; MULTIPLE SULFATASE DEFICIENCY; MPS IVA; Research & Experimental Medicine; DIAGNOSTIC-TEST; Morquio A; Science & Technology; Genetics & Heredity
• Research Categories: Biology, Cell; Biology, Genetics; Chemistry, Biochemistry

Abstract

Morquio A (Mucopolysaccharidosis IVA; MPS IVA) is an autosomal recessive lysosomal storage disorder caused by partial or total deficiency of the enzyme galactosamine-6-sulfate sulfatase (GALNS; also known as N-acetylgalactosamine-6-sulfate sulfatase) encoded by the GALNS gene. Patients who inherit two mutated GALNS gene alleles have a decreased ability to degrade the glycosaminoglycans (GAGs) keratan sulfate and chondroitin 6-sulfate, thereby causing GAG accumulation within lysosomes and consequently pleiotropic disease. GALNS mutations occur throughout the gene and many mutations are identified only in single patients or families, causing difficulties both in mutation detection and interpretation. In this study, molecular analysis of 163 patients with Morquio A identified 99 unique mutations in the GALNS gene believed to negatively impact GALNS protein function, of which 39 are previously unpublished, together with 26 single-nucleotide polymorphisms. Recommendations for the molecular testing of patients, clear reporting of sequence findings, and interpretation of sequencing data are provided.