title: Molecular testing of 163 patients with Morquio A (Mucopolysaccharidosis IVA) identifies 39 novel GALNS mutations.
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99 unique mutations in the GALNS gene believed to negatively impact GALNS protein function, of which 39 are previously unpublished, together with 26 single-nucleotide polymorphisms.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.
authors.affiliation: Molecular and Cell Biology Laboratory, Pediatric Neurology Unit and Laboratories, Meyer Children's Hospital, Florence, Italy; Department of Neurosciences, Psychology, Pharmacology and Child Health, University of Florence, Florence Italy.
authors.forename: A
authors.initials: A
authors.lastname: Morrone
authors.affiliation: Willink Biochemical Genetics, Central Manchester University Hospitals NHS Foundation Trust, Saint Mary's Hospital Oxford Road, Manchester, UK.
authors.forename: K L
authors.initials: KL
authors.lastname: Tylee
authors.affiliation: Department of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: M
authors.initials: M
authors.lastname: Al-Sayed
authors.affiliation: Laboratório de Genética Molecular, Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
authors.forename: A C
authors.initials: AC
authors.lastname: Brusius-Facchin
authors.affiliation: Molecular and Cell Biology Laboratory, Pediatric Neurology Unit and Laboratories, Meyer Children's Hospital, Florence, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Caciotti
authors.affiliation: Willink Biochemical Genetics, Central Manchester University Hospitals NHS Foundation Trust, Saint Mary's Hospital Oxford Road, Manchester, UK.
authors.forename: H J
authors.initials: HJ
authors.lastname: Church
authors.affiliation: Sección de Errores Congénitos del Metabolismo-IBC, Servicio de Bioquímica y Genética Molecular, Hospital Clínic, CIBERER, IDIBAPS, Barcelona, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Coll
authors.affiliation: BioMarin Pharmaceutical Inc., Novato, CA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Davidson
authors.affiliation: SA Pathology, Women's and Children's Hospital, North Adelaide, SA, Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Fietz
authors.affiliation: Sección de Errores Congénitos del Metabolismo-IBC, Servicio de Bioquímica y Genética Molecular, Hospital Clínic, CIBERER, IDIBAPS, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Gort
authors.affiliation: Emory Genetics Laboratory, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hegde
authors.affiliation: Laboratório de Genética Molecular, Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
authors.forename: F
authors.initials: F
authors.lastname: Kubaski
authors.affiliation: Unidade de Bioquímica Genética, Centro de Genética Médica Jacinto Magalhães (CGMJM) do Centro Hospitalar do Porto (CHP), Porto, Portugal.
authors.forename: L
authors.initials: L
authors.lastname: Lacerda
authors.affiliation: Unidade de Bioquímica Genética, Centro de Genética Médica Jacinto Magalhães (CGMJM) do Centro Hospitalar do Porto (CHP), Porto, Portugal.
authors.forename: F
authors.initials: F
authors.lastname: Laranjeira
authors.affiliation: Laboratório de Genética Molecular, Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
authors.forename: S
authors.initials: S
authors.lastname: Leistner-Segal
authors.affiliation: The Buck Institute for Research on Aging, Novato, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Mooney
authors.affiliation: Sección de Errores Congénitos del Metabolismo-IBC, Servicio de Bioquímica y Genética Molecular, Hospital Clínic, CIBERER, IDIBAPS, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Pajares
authors.affiliation: Biochemical Genetics Laboratory, Greenwood Genetic Center, Greenwood, SC, USA.
authors.forename: L
authors.initials: L
authors.lastname: Pollard
authors.affiliation: Unidade de Bioquímica Genética, Centro de Genética Médica Jacinto Magalhães (CGMJM) do Centro Hospitalar do Porto (CHP), Porto, Portugal.
authors.forename: I
authors.initials: I
authors.lastname: Ribeiro
authors.affiliation: Children's Hospital of Orange County, Orange, CA, USA.
authors.forename: R Y
authors.initials: RY
authors.lastname: Wang
authors.affiliation: BioMarin Pharmaceutical Inc., Novato, CA, USA. Electronic address: NMiller@bmrn.com.
authors.forename: N
authors.initials: N
authors.lastname: Miller
mesh_terms: D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D002811:Chondroitinsulfatases / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D056726:Genetic Association Studies; D005820:Genetic Testing; D005838:Genotype; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007223:Infant; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D009085:Mucopolysaccharidosis IV / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D020641:Polymorphism, Single Nucleotide
chemical_list: D006025:Glycosaminoglycans; D002811:Chondroitinsulfatases; C102295:GALNS protein, human
keywords: GALNS; Lysosomal storage disorder; MPS IVA; Morquio A; Mucopolysaccharidosis type IVA; Mutation
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