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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

Green, P. M. ; Montandon, A. J. ; Ljung, R. LU orcid ; Bentley, D. R. ; Nilsson, Inga Marie ; Kling, S. LU and Giannelli, F. (1991) In British Journal of Haematology 78(3). p.390-397
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... (More)

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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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
British Journal of Haematology
volume
78
issue
3
pages
390 - 397
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:1873221
  • scopus:0025733518
ISSN
0007-1048
DOI
10.1111/j.1365-2141.1991.tb04453.x
language
English
LU publication?
yes
id
7e679423-6ef3-4f6b-89a5-cc7d7a0c8c4e
date added to LUP
2016-11-08 15:11:23
date last changed
2025-04-04 14:01:09
@article{7e679423-6ef3-4f6b-89a5-cc7d7a0c8c4e,
  abstract     = {{<p>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 (His<sub>257</sub>→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.</p>}},
  author       = {{Green, P. M. and Montandon, A. J. and Ljung, R. and Bentley, D. R. and Nilsson, Inga Marie and Kling, S. and Giannelli, F.}},
  issn         = {{0007-1048}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{390--397}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{British Journal of Haematology}},
  title        = {{Haemophilia B mutations in a complete Swedish population sample : a test of new strategy for the genetic counselling of diseases with high mutational heterogeneity}},
  url          = {{http://dx.doi.org/10.1111/j.1365-2141.1991.tb04453.x}},
  doi          = {{10.1111/j.1365-2141.1991.tb04453.x}},
  volume       = {{78}},
  year         = {{1991}},
}