A novel mutation in the FGB: c.1105C>T turns the codon for amino acid Bß Q339 into a stop codon causing hypofibrinogenemia.
Blood Cells Mol Dis
; 50(3): 177-81, 2013 Mar.
Article
en En
| MEDLINE
| ID: mdl-23266225
ABSTRACT
Routine coagulation tests on a 14year-old male with frequent epistaxis showed a prolonged thrombin time together with diminished functional (162mg/dl) and gravimetric (122mg/dl) fibrinogen concentrations. His father showed similar aberrant results and sequencing of the three fibrinogen genes revealed a novel heterozygous nonsense mutation in the FGB gene c.1105C>T, which converts the codon for residue Bß 339Q to stop, causing deletion of Bß chain residues 339-461. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and RP-HPLC (reverse-phase high-pressure liquid chromatography) of purified fibrinogen showed only normal Aα, Bß, and γ chains, indicating that molecules with the truncated 37,990Da ß chain were not secreted into plasma. Functional analysis showed impaired fibrin polymerization, fibrin porosity, and elasticity compared to controls. By laser scanning confocal microscopy the patient's fibers were slightly thinner than normal. Electrospray ionization mass spectrometry (ESI MS) presented normal sialylation of the oligosaccharide chains, and liver function tests showed no evidence of liver dysfunction that might explain the functional abnormalities.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fibrinógeno
/
Codón sin Sentido
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Afibrinogenemia
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Mutación
Tipo de estudio:
Diagnostic_studies
Límite:
Adolescent
/
Humans
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Male
Idioma:
En
Revista:
Blood Cells Mol Dis
Asunto de la revista:
HEMATOLOGIA
Año:
2013
Tipo del documento:
Article