PMID- 18801168
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20110714
LR  - 20200929
IS  - 1755-8166 (Electronic)
IS  - 1755-8166 (Linking)
VI  - 1
DP  - 2008 Sep 18
TI  - On the origin of trisomy 21 Down syndrome.
PG  - 21
LID - 10.1186/1755-8166-1-21 [doi]
AB  - 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.
FAU - Hulten, Maj A
AU  - Hulten MA
AD  - Warwick Medical School, University of Warwick, UK. maj.hulten@warwick.ac.uk.
FAU - Patel, Suketu D
AU  - Patel SD
FAU - Tankimanova, Maira
AU  - Tankimanova M
FAU - Westgren, Magnus
AU  - Westgren M
FAU - Papadogiannakis, Nikos
AU  - Papadogiannakis N
FAU - Jonsson, Anna Maria
AU  - Jonsson AM
FAU - Iwarsson, Erik
AU  - Iwarsson E
LA  - eng
PT  - Journal Article
DEP - 20080918
PL  - England
TA  - Mol Cytogenet
JT  - Molecular cytogenetics
JID - 101317942
PMC - PMC2564957
EDAT- 2008/09/20 09:00
MHDA- 2008/09/20 09:01
PMCR- 2008/09/18
CRDT- 2008/09/20 09:00
PHST- 2008/08/27 00:00 [received]
PHST- 2008/09/18 00:00 [accepted]
PHST- 2008/09/20 09:00 [pubmed]
PHST- 2008/09/20 09:01 [medline]
PHST- 2008/09/20 09:00 [entrez]
PHST- 2008/09/18 00:00 [pmc-release]
AID - 1755-8166-1-21 [pii]
AID - 10.1186/1755-8166-1-21 [doi]
PST - epublish
SO  - Mol Cytogenet. 2008 Sep 18;1:21. doi: 10.1186/1755-8166-1-21.