Adverse Effects of Trichothiodystrophy DNA Repair and Transcription Gene Abnormalities on Human Fetal Development
Abstract The effects of DNA repair and transcription genes in human prenatal life have never been studied. Trichothiodystrophy (TTD) is a rare (affected frequency of 10^-6^) recessive disorder caused by mutations in genes involved in the nucleotide excision repair (NER) pathway and in transcription....
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Published in | Nature precedings |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
11.08.2009
|
Online Access | Get full text |
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Summary: | Abstract
The effects of DNA repair and transcription genes in human prenatal life have never been studied. Trichothiodystrophy (TTD) is a rare (affected frequency of 10^-6^) recessive disorder caused by mutations in genes involved in the nucleotide excision repair (NER) pathway and in transcription. Based on our clinical observations, we conducted a genetic epidemiologic study to investigate gestational outcomes associated with TTD. We compared pregnancies resulting in TTD-affected offspring (N=24) with respect to abnormalities in their antenatal and neonatal periods to pregnancies resulting in their unaffected siblings (N=18), accounting for correlation, and to population reference values. Significantly higher incidence of several severe gestational complications was noted in TTD-affected pregnancies. Gestational complications were noted in nearly all pregnancies resulting in TTD-affected offspring with
XPD
and
TTDN1
, but not
TTD-A
, gene mutations. Abnormal placental development may explain the constellation of observed complications; therefore, we hypothesize that some TTD genes play an important role in normal placental and fetal development. We investigated this hypothesis by analyzing the expression patterns of TTD genes. Expression of
TTDA
was strongly negatively correlated (r=-0.7,P<0.0001) with gestational age, while
XPD, XPB
and
TTDN1
were consistently expressed from 14 to 40 weeks gestation. *Conclusion:* Our results indicate an important role for
XPD, XPB
and
TTDN1
gene products during normal human placental and fetal development. |
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ISSN: | 1756-0357 1756-0357 |
DOI: | 10.1038/npre.2009.3582.1 |