title: Genotypes and phenotypes of patients in the UK with carbohydrate-deficient glycoprotein syndrome type 1.
abstract: 18 UK patients (14 families) have been diagnosed with the carbohydrate-deficient glycoprotein syndrome (CDGS), type 1, on the basis of their clinical symptoms and/or abnormal electrophoretic patterns of serum transferrin. Eleven out of the 16 infants died before the age of 2 years. Patients from 12 families had a typical type 1 transferrin profile but one had a variant profile and another, who had many of the clinical features of CDGS type 1, had a normal profile. Eleven of the patients (10 families) with the typical type 1 profile had a deficiency of phosphomannomutase (PMM), (CDGS type 1a) but there was no correlation between residual enzyme activity and severity of disease. All these patients were compound heterozygotes for mutations in the phosphomannomutase (PMM2) gene, with 7 out of the 10 families having the common R141H mutation. Eight different mutations were found, including three novel ones. There was no correlation between genotype and phenotype, although siblings had similar phenotypes. Three patients, including the one with the normal transferrin profile, did not have a deficiency of phosphomannomutase or phosphomannose isomerase (CDGS 1b).
authors.affiliation: Biochemistry, Endocrinology and Metabolism Unit, Institute of Child Health (University College London), UK.
authors.forename: F
authors.initials: F
authors.lastname: Imtiaz
authors.forename: V
authors.initials: V
authors.lastname: Worthington
authors.forename: M
authors.initials: M
authors.lastname: Champion
authors.forename: C
authors.initials: C
authors.lastname: Beesley
authors.forename: J
authors.initials: J
authors.lastname: Charlwood
authors.forename: P
authors.initials: P
authors.lastname: Clayton
authors.forename: G
authors.initials: G
authors.lastname: Keir
authors.forename: N
authors.initials: N
authors.lastname: Mian
authors.forename: B
authors.initials: B
authors.lastname: Winchester
mesh_terms: D002478:Cells, Cultured; D018981:Congenital Disorders of Glycosylation / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D004252:DNA Mutational Analysis; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008214:Lymphocytes / Q000201:enzymology; D008297:Male; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014168:Transferrin / Q000235:genetics / Q000378:metabolism
chemical_list: D014168:Transferrin