| 1. |
- 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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| 2. |
- Kling, S., et al.
(författare)
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Origin of mutation in sporadic cases of haemophilia-B
- 1992
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 48:3, s. 142-145
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Tidskriftsartikel (refereegranskat)abstract
- Of the 45 haemophilia-B patients registered at the haemophilia centre in Malmo, Sweden, 24 are the sole members of their families to be affected, and in 13 of these 24 cases, ascendant relatives are available for study. Detection of the gene defect showed the mutation to be de novo in the proband in 3 of these 13 cases, and inherited from a carrier mother in the remaining 10 cases. All 10 carrier mothers were shown to have de novo mutations, as the patients' grandfathers were phenotypically and/or haematologically normal, and the grandmothers were non-carriers. Seven restriction fragment length polymorphisms (RFLPs) of the factor IX gene were used to determine whether the de novo mutations of the 10 carrier mothers were of paternal or maternal origin. In 6/10 cases, the RFLP patterns were informative, and indicated the mutation to be of paternal origin.
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| 3. |
- Landin, B., et al.
(författare)
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Haemoglobin Koln as de novo mutations in Sweden : Diagnosis by PCR and specific enzymatic cleavage
- 1994
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 52:3, s. 156-161
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Tidskriftsartikel (refereegranskat)abstract
- Three independent cases of chronic haemolytic anaemia in Sweden have recently been demonstrated to be due to the unstable haemoglobin variant Hb Koln. The patients, all of whom have partially compensated chronic haemolytic anaemia, presented with aggravated haemolysis during acute infections in childhood. In one case, acute B19 parvovirus infection induced an aplastic crisis. The substitutions all seem to have occurred as de novo mutations. Diagnosis was based on haemoglobin instability testing and isoelectric focusing of haemoglobin dimers. The final identification procedure for the substitutions included extraction of DNA from whole blood, polymerase chain reaction (PCR) amplification of parts of the β-globin gene and nucleotide sequencing of the resulting material, or studies of restriction length polymorphisms (RFLPs) using the restriction endonucleases Mae II or Nla III. The use of PCR-RFLP is recommended as a valuable tool for diagnosing Hb Koln.
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| 4. |
- Ljung, R., et al.
(författare)
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Antenatal diagnosis of haemophilia B by amplification and electrophoresis of an exon fragment with a short deletion
- 1992
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Ingår i: European Journal of Haematology. - 0902-4441. ; 49:4, s. 215-218
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Tidskriftsartikel (refereegranskat)abstract
- Cartier identification and antenatal diagnosis were performed in 2 sisters by electrophoretic separation of the normal and abnormal bands obtained after amplification of a fragment of exon h in the factor IX gene. The mutation in the family had been characterised as an 8-base pair (bp) deletion in exon h. By amplification of a 326 bp fragment containing the site of deletion, the shorter 318 bp band of the haemophilia B gene could be separated by electrophoresis of the fragments. The comprehensive data collection at the Haemophila Centre is of vital importance in the genetic counselling of haemophilia families, and was a crucial step for the successful diagnoses in these sisters.
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| 5. |
- Ljung, R., et al.
(författare)
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Inversions of the factor VIII gene in Swedish patients with severe haemophilia A
- 1995
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 54:5, s. 310-313
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Tidskriftsartikel (refereegranskat)abstract
- The series comprised 49 Swedish patients with severe haemophilia G [belonging to 49 families (21 with known and 28 with sporadic haemophilia)l, of whom 12 had developed F.VIII inhibitors. Using Southern blotting, 45% (22/49) were found to have inversions, i.e., intrachromosomal rearrangements of the tip of the X chromosome. Twenty patients had one or the other of the two variants of inversions recently published, whereas 2 patients manifested novel band patterns. Inversions were found in 50% of the families with sporadic haemophilia, and in 38% of those with known haemophilia. Fourteen families with sporadic haemophilia A had inversions, the proband carrying the de novo mutation in 4 cases and the proband's mother in 10 cases. Six inversions derived from a male and five from a female X-chromosome meiosis, the origin of the remaining three was not established. Genetic counselling of patients with severe haemophilia A and their families will be considerably improved, as inversions occur in half the severe cases and can be detected by a simple Southern blotting procedure.
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