Identification of two novel mutations in non-Jewish factor XI deficiency
| Autor: | T Nishimura, K. Lal, Jh Mcvey, Egd Tuddenham, Paula H. B. Bolton-Maggs, Yasufumi Imanaka |
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| Rok vydání: | 1995 |
| Předmět: |
Adult
Male Factor XI Deficiency DNA Mutational Analysis Molecular Sequence Data Nonsense mutation Biology medicine.disease_cause Exon medicine Humans Missense mutation Blood Coagulation Gene Factor XI Genetics Mutation Polymorphism Genetic Base Sequence Transition (genetics) Nucleic acid sequence Single-strand conformation polymorphism Exons Hematology Middle Aged Molecular biology Pedigree Female |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1365-2141 0007-1048 |
| DOI: | 10.1111/j.1365-2141.1995.tb05215.x |
| Popis: | We have studied two heterozygous unrelated CRM- non-Jewish FXI-deficient patients. Neither of the patients carries a previously described mutation. Their FXI genes were screened by SSCP analysis following PCR amplification of each exon and the flanking intronic sequences. DNA fragments showing aberrant mobility were cloned and sequenced. The following mutations were identified: in case 1, a T to G transition in exon 12 results in the substitution of Phe-442 by Val (FXI-F442V); in case 2 a C to A transition in exon 5 results in the substitution of Cys-128 by a nonsense codon (FXI-C128X). The missense mutation results in a substitution within the protease domain of FXI. Molecular modelling locates this residue in a structurally conserved region of the protease domain and the amino acid substitution may therefore interfere with either chain folding and subsequent secretion or the stability of the protein in plasma. We conclude that the mutations which we have identified are responsible for the inherited abnormality in these patients. |
| Databáze: | OpenAIRE |
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