Hypofibrinogenemia in an individual with 2 coding (gamma82 A-->G and Bbeta235 P-->L) and 2 noncoding mutations.
Blood
; 95(5): 1709-13, 2000 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-10688828
ABSTRACT
We investigated the molecular basis of hypofibrinogenemia in a man with a normal thrombin clotting time. Protein analysis indicated equal plasma expression of 2 different Bbeta alleles, and DNA sequencing confirmed heterozygosity for a new Bbeta235 P-->L mutation. Protein analysis also revealed a novel gamma(D) chain, present at a ratio of 12 relative to the gamma(A) chain. Mass spectrometry indicated a 14 d decrease in the gamma(D)-chain mass, and DNA sequencing showed this was caused by a novel gamma82 A-->G substitution. DNA sequencing established heterozygosity for 2 further mutations T-->C in intron 4 of the Aalpha gene and A-->C in the 3' noncoding region of the Bbeta gene. Studies on the man's daughter, together with plasma expression levels, discounted both the Aalpha and Bbeta mutations as the cause of the low fibrinogen, suggesting that the gamma82 mutation caused the hypofibrinogenemia. This was supported by analysis of 31 normal controls in whom the Bbeta mutations were found at polymorphic levels, with an allelic frequency of 5% for the Bbeta235 mutation and 42% for the Bbeta 3' untranslated mutation. The gamma82 mutation was, however, unique to the propositus. Residue gamma82 is located in the triple helix that separates the E and D domains, and aberrant packing of the helices may explain the decreased fibrinogen concentration. (Blood. 2000;951709-1713)
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fibrinogênios Anormais
/
Mutação Puntual
/
Substituição de Aminoácidos
/
Afibrinogenemia
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
Limite:
Aged
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Blood
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Nova Zelândia