title: Morquio A syndrome-associated mutations: a review of alterations in the GALNS gene and a new locus-specific database.
abstract: Morquio A syndrome (mucopolysaccharidosis IVA) is an autosomal recessive disorder that results from deficient activity of the enzyme N-acetylgalactosamine-6-sulfatase (GALNS) due to alterations in the GALNS gene, which causes major skeletal and connective tissue abnormalities and effects on multiple organ systems. The GALNS alterations associated with Morquio A are numerous and heterogeneous, and new alterations are continuously identified. To aid detection and interpretation of GALNS alterations, from previously published research, we provide a comprehensive and up-to-date listing of 277 unique GALNS alterations associated with Morquio A identified from 1,091 published GALNS alleles. In agreement with previous findings, most reported GALNS alterations are missense changes and even the most frequent alterations are relatively uncommon. We found that 48% of patients are assessed as homozygous for a GALNS alteration, 39% are assessed as heterozygous for two identified GALNS alterations, and in 13% of patients only one GALNS alteration is detected. We report here the creation of a locus-specific database for the GALNS gene (http://galns.mutdb.org/) that catalogs all reported alterations in GALNS to date. We highlight the challenges both in alteration detection and genotype-phenotype interpretation caused in part by the heterogeneity of GALNS alterations and provide recommendations for molecular testing of GALNS.
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: Amelia
authors.initials: A
authors.lastname: Morrone
authors.forename: Anna
authors.initials: A
authors.lastname: Caciotti
authors.forename: Robert
authors.initials: R
authors.lastname: Atwood
authors.forename: Kathryn
authors.initials: K
authors.lastname: Davidson
authors.forename: Chaoyi
authors.initials: C
authors.lastname: Du
authors.forename: Patricia
authors.initials: P
authors.lastname: Francis-Lyon
authors.forename: Paul
authors.initials: P
authors.lastname: Harmatz
authors.forename: Matthew
authors.initials: M
authors.lastname: Mealiffe
authors.forename: Sean
authors.initials: S
authors.lastname: Mooney
authors.forename: Tal Ronnen
authors.initials: TR
authors.lastname: Oron
authors.forename: April
authors.initials: A
authors.lastname: Ryles
authors.forename: Karl A
authors.initials: KA
authors.lastname: Zawadzki
authors.forename: Nicole
authors.initials: N
authors.lastname: Miller
mesh_terms: D000483:Alleles; D000818:Animals; D015415:Biomarkers; D002811:Chondroitinsulfatases / Q000235:genetics*; D030561:Databases, Nucleic Acid; D004195:Disease Models, Animal; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D005843:Geography; D006801:Humans; D007231:Infant, Newborn; D009085:Mucopolysaccharidosis IV / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D009154:Mutation; D015997:Neonatal Screening; D010641:Phenotype; D040641:Quantitative Trait Loci
chemical_list: D015415:Biomarkers; D002811:Chondroitinsulfatases; C102295:GALNS protein, human
keywords: GALNS; MPS IVA; Morquio A; lysosomal storage disorder; mucopolysaccharidosis type IVA