title: Biochemical and molecular studies in 26 Spanish patients with congenital disorder of glycosylation type Ia.
abstract: We present our experience with the diagnosis of 26 patients (19 families) with congenital disorders of glycosylation classified as type Ia due to PMM deficiency. In all but one of these CDG Ia families the patients are compound heterozygous for mutations in PMM2. Eighteen different mutations were detected. In contrast to other series in which R141H represents 43-50% of the alleles, only 9/36 (25%) alleles have this mutation. Two mutations (R123Q and T237M) have been found on three disease chromosomes, four (V44A, Y64C, P113L and F207S) on two disease chromosomes and 12 mutations (D65Y, Y76C, IVS3+2C>T, E93A, R123X, V129M, I153T, F157S, E197A, N216I, T226S, C241S) only on one disease chromosome. V44A and D65Y probably originated in the Iberian peninsula, as they have only been reported in Portuguese and Latin-American patients; Y64C, Y76C, R123X and F207S have not been detected in other patients. R123X is the only stop codon mutation so far described in PMM2. The common European F119L mutation has not been found in our patients, although it is very frequent in other populations (43% allele frequency in Danish patients). Probably because of this genetic heterogeneity, Spanish patients show very diverse phenotypes that are, in general, milder than in other series. This points to the necessity of widening the criteria for CDG in the routine screening for inborn metabolic diseases.
authors.affiliation: Institut de Bioquímica Clínica, Corporació Sanitària Clinic, Barcelona, Spain. pbriones@clinic.ub.es
authors.forename: P
authors.initials: P
authors.lastname: Briones
authors.forename: M A
authors.initials: MA
authors.lastname: Vilaseca
authors.forename: E
authors.initials: E
authors.lastname: Schollen
authors.forename: I
authors.initials: I
authors.lastname: Ferrer
authors.forename: M
authors.initials: M
authors.lastname: Maties
authors.forename: C
authors.initials: C
authors.lastname: Busquets
authors.forename: R
authors.initials: R
authors.lastname: Artuch
authors.forename: L
authors.initials: L
authors.lastname: Gort
authors.forename: M
authors.initials: M
authors.lastname: Marco
authors.forename: E
authors.initials: E
authors.lastname: van Schaftingen
authors.forename: G
authors.initials: G
authors.lastname: Matthijs
authors.forename: J
authors.initials: J
authors.lastname: Jaeken
authors.forename: A
authors.initials: A
authors.lastname: Chabás
mesh_terms: D002239:Carbohydrate Metabolism, Inborn Errors / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006031:Glycosylation; D006801:Humans; D007231:Infant, Newborn; D007525:Isoelectric Focusing; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D009154:Mutation / Q000235:genetics; D017875:Phosphotransferases (Phosphomutases) / Q000235:genetics / Q000378:metabolism; D011863:Radioimmunoassay; D012189:Retrospective Studies; D013030:Spain / Q000453:epidemiology; D014168:Transferrin / Q000737:chemistry / Q000235:genetics
chemical_list: D014168:Transferrin; D017875:Phosphotransferases (Phosphomutases); C052799:phosphomannomutase