title: Two novel mutations in the L ferritin coding sequence associated with benign hyperferritinaemia unmasked by glycosylated ferritin assay.
abstract: Investigating persistent hyperferritinaemia without apparent iron overload is challenging. Even when inflammation, cirrhosis, Still's disease, fatty liver and malignancy are excluded, there remains a group of patients with unexplained hyperferritinaemia for whom rare forms of haemochromatosis (ferroportin disease) are a consideration. Preliminary results suggest that abnormal percentage glycosylation of serum ferritin is seen in some cases of genetically determined hyperferritinaemia. Serum ferritin is normally 50-81% glycosylated, but low glycosylation (20-42%) prevails in hereditary hyperferritinaemia cataract syndrome. This contrasts with hyperglycosylation (>90%) associated with the benign hyperferritinaemia related to missense L ferritin (p.Thr30Ile) mutation. Here, we describe two novel missense L ferritin variants also associated with hyperglycosylation, p.Gln26Ile and p.Ala27Val. Ferritin glycosylation, a comparatively simple measurement, can identify patients for DNA sequencing as hyperglycosylation (>90%) is associated with benign hyperferritinaemia and mutant L ferritin chain.
authors.affiliation: Department of Pathology, Princess Royal University Hospital, Farnborough, Orpington, Kent BR6 8ND, UK. vanessa.thurlow@gmail.com
authors.forename: Vanessa
authors.initials: V
authors.lastname: Thurlow
authors.forename: Bipin
authors.initials: B
authors.lastname: Vadher
authors.forename: Adrian
authors.initials: A
authors.lastname: Bomford
authors.forename: Corinne
authors.initials: C
authors.lastname: DeLord
authors.forename: Caroline
authors.initials: C
authors.lastname: Kannengiesser
authors.forename: Carole
authors.initials: C
authors.lastname: Beaumont
authors.forename: Bernard
authors.initials: B
authors.lastname: Grandchamp
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D001052:Apoferritins / Q000097:blood / Q000235:genetics*; D005293:Ferritins / Q000097:blood / Q000235:genetics*; D006031:Glycosylation; D006801:Humans; D019189:Iron Metabolism Disorders / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D016366:Open Reading Frames; D017422:Sequence Analysis, DNA; D006023:Glycoproteins
chemical_list: D001052:Apoferritins; D005293:Ferritins; C051036:glycosylated ferritin; D006023:Glycoproteins