hkr.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Origin of mutation in sporadic cases of severe haemophilia A in Sweden
Lund University.
Lund University.
Lund University.
Kristianstad University, School of Education and Environment, Avdelningen för Naturvetenskap. Kristianstad University, Plattformen för molekylär analys.
Show others and affiliations
2016 (English)In: Clinical Genetics, ISSN 0009-9163, E-ISSN 1399-0004, Vol. 90, no 1, 63-68 p.Article in journal (Refereed) Published
Abstract [en]

Many newly diagnosed Swedish severe haemophilia A (HA) patients are sporadic cases. Some genotypically non-carrier mothers have gone on to have two descendants with the same mutation, presumably because of mosaicism.

AIMS: To define the origin of mutation in sporadic cases of HA, reveal possible sex-specific differences in mutagenesis and identify potential mosaics among non-carrier mothers.

METHOD: Sanger sequencing characterized the mutations and microsatellite haplotyping determined the origin of the X chromosome carrying the mutation in 3 generations of 45 families with sporadic severe HA. Droplet digital polymerase chain reaction (ddPCR) was used in five cases to reveal that mosaicism mutations are not found on conventional DNA sequencing.

RESULTS: In 23 out of 45 families, the mother carried the mutation and in 5 out of 28 families, the grandmother was also a carrier. The X chromosome was of grandpaternal origin in 17 out of 23 cases. One of five tested mothers was a mosaic with a mutation frequency of 7%.

CONCLUSION: In 40 out of 45 families, the sporadic case resulted from a mutation in the last two generations. In 82% (23/28), the carrier mothers had a de novo mutation where the X chromosome was of paternal origin in 74% (17/23). ddPCR is a potentially powerful and promising analysis for mosaicism in HA.

Place, publisher, year, edition, pages
2016. Vol. 90, no 1, 63-68 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:hkr:diva-16090DOI: 10.1111/cge.12709ISI: 000378652000008PubMedID: 26661908OAI: oai:DiVA.org:hkr-16090DiVA: diva2:975030
Funder
Swedish Research Council, K2013-64X-22298-01-03Region Skåne
Available from: 2016-09-28 Created: 2016-09-28 Last updated: 2017-02-28Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Manderstedt, EricHalldén, Christer
By organisation
Avdelningen för NaturvetenskapPlattformen för molekylär analys
In the same journal
Clinical Genetics
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 16 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf