Hypofibrinogenaemia with compound heterozygosity for two gamma chain mutations - gamma 82 Ala--Gly and an intron two GT--AT splice site mutation

Autor:	J, Wyatt, S O, Brennan, S, May, P M, George
Rok vydání:	2000
Předmět:	Adult Family Health Male Heterozygote Base Sequence DNA Mutational Analysis Pregnancy Complications Hematologic Fibrinogen Hemorrhage Afibrinogenemia Introns Phenotype Amino Acid Substitution Codon Nonsense Pregnancy Mutation Humans Point Mutation Female RNA Splice Sites
Zdroj:	Thrombosis and haemostasis. 84(3)
ISSN:	0340-6245
Popis:	We investigated the molecular basis of hypofibrinogenaemia in a woman with a history of recurrent, pregnancy-associated bleeding, and miscarriage. She had a Clauss fibrinogen of 0.9 mg/ml and SDS PAGE of purified fibrinogen showed a normal pattern of chains. However careful inspection of reverse phase chain separation profiles showed apparent homozygosity for a more hydrophilic form of the gamma chain. DNA Sequencing showed only heterozygosity for a CGT--GGT (Ala--Gly) mutation at codon gamma82, but further sequencing showed an additional GT splice sequence mutation at the 5' end of intron 2 of the gamma gene. Translation of mRNA containing this intron would result in premature truncation explaining the phenotypic homozygosity of the gamma82 Ala--Gly substitution. The patient's sister had a mild bleeding disorder with hypofibrinogenaemia and she too was a compound heterozygote for the y mutations. Her nephew had only the novel splice site mutation, while her mother and daughter inherited only the gamma82 Ala--Gly substitution.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=pmid________::471019a7d629392d128e85c66cb20386 https://pubmed.ncbi.nlm.nih.gov/11019970 Zobrazit plný text záznamu