Creation of a novel donor splice site in intron 1 of the factor VIII gene leads to activation of a 191 bp cryptic exon in two haemophilia A patients

Autor:	Francesco Giannelli, B. T. Colvin, Christine Lee, Peter M. Green, Richard Bagnall, Naushin Waseem
Rok vydání:	1999
Předmět:	Genetics congenital hereditary and neonatal diseases and abnormalities Mutation Splice site mutation Point mutation Haemophilia A Intron Hematology Biology medicine.disease_cause medicine.disease Molecular biology Exon hemic and lymphatic diseases medicine Coding region Gene
Zdroj:	British Journal of Haematology. 107:766-771
ISSN:	0007-1048
Popis:	Summary. We have constructed a confidential U.K. database of haemophilia A mutations and pedigrees by characterizing the gene defect of one index patient in each U.K. family. Mutations were identified by screening all coding regions of the factor VIII (FVIII) mRNA, using solid-phase fluorescent chemical cleavage of mismatch and examining additional non-coding regions of the gene. Here we report two haemophilia A patients (UK 114 FVIII:C 2% and UK 243 FVIII:C < 1%) with an abnormal FVIII mRNA due to an A to G point mutation, 1·4 kb downstream from exon 1 in the FVIII gene. This mutation creates a new donor splice site in intron 1 and leads to insertion of a 191 bp novel exon in the mRNA. Haplotype analysis suggests that the mutation may have originated in a common ancestor of the two patients, who further illustrate how mRNA analysis allows higher efficiency of haemophilia A mutation detection, because their mutation would not have been identified by direct analysis of the factor VIII gene.
Databáze:	OpenAIRE
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