caa a22 4500 467985952 CHVBK 20180323112532.0 cr unu---uuuuu 170328e19900701xx s 000 0 eng 10.1007/BF00193196 doi (NATIONALLICENCE)springer-10.1007/BF00193196 Two factor IX mutations in the family of an isolated haemophilia B patient: direct carrier diagnosis by amplification mismatch detection (AMD) [Elektronische Daten] [A. Montandon, P. Green, D. Bentley, R. Ljung, I. Nilsson, F. Giannelli] Summary: Rapid identification of gene defects allows definite carrier and prenatal diagnosis in virtually every family with haemophilia B. We report a study of the family of an isolated patient. Analysis of all the essential regions of the patient's factor IX gene (promoter, exons, transcript processing signals) revealed two mutations: one C→T transition at residue 17762 and another at residue 30890. The former created a translation stop at codon 116, and the latter caused substitution of His 257 by Tyr. The translation stop is an obvious detrimental mutation, while the His 257→Tyr substitution has uncertain functional consequences. From analysis of other family members, it was found that the first mutation had occurred at grandpaternal gametogenesis, in keeping with the negative family history, while the second was of more remote origin and did not reduce the maternal grandfather's factor IX coagulant and antigen level. This neutral mutation (His 257→Tyr) pinpoints a poorly conserved amino acid in factor IX and related serine proteases. Its coexistence with a detrimental mutation stresses the need to examine all essential regions of a gene before attempting to interpret the functional consequences of its sequence changes. Springer-Verlag, 1990 Montandon A. Paediatric Research Unit, Division of Medical and Molecular Genetics, United Medical and Dental Schools of Guy's and St. Thomas's Hospitals, 8th Floor Guy's Hospital Tower, London Bridge, SE1 9RT, London, UK aut Green P. Paediatric Research Unit, Division of Medical and Molecular Genetics, United Medical and Dental Schools of Guy's and St. Thomas's Hospitals, 8th Floor Guy's Hospital Tower, London Bridge, SE1 9RT, London, UK aut Bentley D. Paediatric Research Unit, Division of Medical and Molecular Genetics, United Medical and Dental Schools of Guy's and St. Thomas's Hospitals, 8th Floor Guy's Hospital Tower, London Bridge, SE1 9RT, London, UK aut Ljung R. Department of Coagulation Disorders, University of Lund, Malmö General Hospital, S-21401, Malmö, Sweden aut Nilsson I. Department of Coagulation Disorders, University of Lund, Malmö General Hospital, S-21401, Malmö, Sweden aut Giannelli F. Paediatric Research Unit, Division of Medical and Molecular Genetics, United Medical and Dental Schools of Guy's and St. Thomas's Hospitals, 8th Floor Guy's Hospital Tower, London Bridge, SE1 9RT, London, UK aut Human Genetics Springer-Verlag 85/2(1990-07-01), 200-204 0340-6717 85:2<200 1990 85 439 https://doi.org/10.1007/BF00193196 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00193196 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Montandon A. Paediatric Research Unit, Division of Medical and Molecular Genetics, United Medical and Dental Schools of Guy's and St. Thomas's Hospitals, 8th Floor Guy's Hospital Tower, London Bridge, SE1 9RT, London, UK aut NATIONALLICENCE 700 1- Green P. Paediatric Research Unit, Division of Medical and Molecular Genetics, United Medical and Dental Schools of Guy's and St. Thomas's Hospitals, 8th Floor Guy's Hospital Tower, London Bridge, SE1 9RT, London, UK aut NATIONALLICENCE 700 1- Bentley D. Paediatric Research Unit, Division of Medical and Molecular Genetics, United Medical and Dental Schools of Guy's and St. Thomas's Hospitals, 8th Floor Guy's Hospital Tower, London Bridge, SE1 9RT, London, UK aut NATIONALLICENCE 700 1- Ljung R. Department of Coagulation Disorders, University of Lund, Malmö General Hospital, S-21401, Malmö, Sweden aut NATIONALLICENCE 700 1- Nilsson I. Department of Coagulation Disorders, University of Lund, Malmö General Hospital, S-21401, Malmö, Sweden aut NATIONALLICENCE 700 1- Giannelli F. Paediatric Research Unit, Division of Medical and Molecular Genetics, United Medical and Dental Schools of Guy's and St. Thomas's Hospitals, 8th Floor Guy's Hospital Tower, London Bridge, SE1 9RT, London, UK aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 85/2(1990-07-01), 200-204 0340-6717 85:2<200 1990 85 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer