Hultén, Maj A., Patel, Suketu D., Tankimanova, Maira, Westgren, Magnus, Papadogiannakis, Nikos, Jonsson, Anna Maria and Iwarsson, Erik. (2008) On the origin of trisomy 21 Down syndrome. Molecular Cytogenetics, Vol.1 (No.21). ISSN 1755-8166

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Abstract

Background: Down syndrome, characterized by an extra chromosome 21 is the most common genetic cause for congenital malformations and learning disability. It is well known that the extra chromosome 21 most often originates from the mother, the incidence increases with maternal age, there may be aberrant maternal chromosome 21 recombination and there is a higher recurrence in young women. In spite of intensive efforts to understand the underlying reason(s) for these characteristics, the origin still remains unknown. We hypothesize that maternal trisomy 21 ovarian mosaicism might provide the major causative factor. Results: We used fluorescence in situ hybridization (FISH) with two chromosome 21-specific probes to determine the copy number of chromosome 21 in ovarian cells from eight female foetuses at gestational age 14–22 weeks. All eight phenotypically normal female foetuses were found to be mosaics, containing ovarian cells with an extra chromosome 21. Trisomy 21 occurred with about the same frequency in cells that had entered meiosis as in pre-meiotic and ovarian mesenchymal stroma cells. Conclusion: We suggest that most normal female foetuses are trisomy 21 ovarian mosaics and the maternal age effect is caused by differential selection of these cells during foetal and postnatal development until ovulation. The exceptional occurrence of high-grade ovarian mosaicism may explain why some women have a child with Down syndrome already at young age as well as the associated increased incidence at subsequent conceptions. We also propose that our findings may explain the aberrant maternal recombination patterns previously found by family linkage analysis.

Item Type:	Journal Article
Subjects:	R Medicine > R Medicine (General)
Divisions:	Faculty of Medicine > Warwick Medical School > Clinical Sciences Research Institute (CSRI) Faculty of Medicine > Warwick Medical School > Reproductive Health Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Down syndrome, Human chromosome abnormalities, Mosaicism
Journal or Publication Title:	Molecular Cytogenetics
Publisher:	BioMed Central Ltd.
ISSN:	1755-8166
Date:	18 September 2008
Volume:	Vol.1
Number:	No.21
Identification Number:	10.1186/1755-8166-1-21
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
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URI:	http://wrap.warwick.ac.uk/id/eprint/536

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