| 1. |
- Green, P. M., et al.
(författare)
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Haemophilia B mutations in a complete Swedish population sample : a test of new strategy for the genetic counselling of diseases with high mutational heterogeneity
- 1991
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 78:3, s. 390-397
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Tidskriftsartikel (refereegranskat)abstract
- Carrier and prenatal diagnosis based on the identification of the gene defect (direct diagnosis) increases the proportion of haemophilia B families that can be offered precise genetic counselling from the 50-60% attainable by DNA markers, to 100%, and they also provide information on the molecular biology of the disease. We propose that in order to maximize the practical and scientific benefits of direct diagnosis the gene defect of complete (possibly national) populations of patients should be characterized and the information stored in appropriate confidential databases. We demonstrate the feasibility of such a strategy by characterizing the mutations of all the patients registered with the Malmo haemophilia centre. These patients (44♂ and 1♀) are from 45 unrelated families and 24 (53%) have negative family history. The 25 patients with similar reduction of factor IX:C and factor IX:Ag (24♂ + 1♀) have: two gross deletions, three frameshifts, four translation stops, six mutations expected to affect pre-mRNA splicing and 10 amino acid substitutions. The six patients with greater reduction of factor IX:C than factor IX:Ag and the seven with reduced IX:C and normal IX:Ag have only amino acid substitutions. Patients with inhibitors have: one complete deletion, one frameshift and three translation stops. One patient has both a translation stop and a functionally neutral amino acid substitution (His257→Tyr). Characterization of the factor IX mutation was successful in every case, usually entailed 4 person-days work, and has led to the identification of 12 amino acid residues essential for the factor IX structure and function.
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| 2. |
- Kling, S., et al.
(författare)
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Moderate haemophilia B in a female carrier caused by preferential inactivation of the paternal X chromosome
- 1991
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 47:4, s. 257-261
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Tidskriftsartikel (refereegranskat)abstract
- The case of a female with moderate haemophilia B is reported. She is the only affected member of her family, and factor IX RFLP analysis shows her to have inherited no maternal markers for polymorphisms located in the first intron and 8 Kb 3' of the polyadenylation signal (DdeI and HhaI, respectively). This clearly indicates a deletion involving at least the last 7 exons of the factor IX gene. Her other factor IX gene inherited from her healthy father is normal as her son is also healthy. This suggests the patient's haemophilia to be due to gross bias in the proportion of factor IX-producing cells with an inactive paternal X chromosome. Methylation studies on the 5' region of the PGK gene show that virtually all the patient's lymphocytes carry a hypermethylated and presumably an inactive paternal X chromosome. The reason for this bias in the activity of her two X chromosomes is not clear, as no chromosomal alterations were found.
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| 3. |
- Montandon, A. J., et al.
(författare)
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A new strategy for carrier and prenatal diagnosis and molecular studies in haemophilia B
- 1991
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Ingår i: Biotechnology of Plasma Proteins : Haemostasis, Thrombosis and Iron Proteins International Symposium, Florence, April 1990 - Haemostasis, Thrombosis and Iron Proteins International Symposium, Florence, April 1990. - : S. Karger AG. - 9783805552509 - 9783318035285 ; 58, s. 88-93
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Konferensbidrag (refereegranskat)
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