Document Detail

Adverse effects of trichothiodystrophy DNA repair and transcription gene disorder on human fetal development.
MedLine Citation:
PMID:  20002457     Owner:  NLM     Status:  MEDLINE    
The effects of DNA repair and transcription gene abnormalities in human pre-natal life have never been studied. Trichothiodystrophy (TTD) is a rare (affected frequency of 10(-6)) recessive disorder caused by mutations in genes involved in nucleotide excision repair (NER) pathway and in transcription. Based on our novel 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 during 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. Small for gestational age (SGA) <10th percentile [Relative risk (RR ) = 9.3, 95% CI = 1.4-60.5, p = 0.02], SGA <3rd percentile (RR = 7.2, 95% CI = 1.1-48.1, p = 0.04), and neonatal intensive care unit (NICU) hospitalization (RR = 6.4, 95% CI = 1.4-29.5, p = 0.02) occurred more frequently among TTD-affected neonates compared with their unaffected siblings. Compared with reference values from general obstetrical population, pregnancies that resulted in TTD-affected infants were significantly more likely to be complicated by hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome (RR = 35.7, 95% CI = 7.6-92.5, p = 0.0002), elevated mid-trimester maternal serum human chorionic gonadotropin (hCG) levels (RR = 14.3, 95% CI = 7.0-16.6, p < 0.0001), SGA <3rd percentile (RR = 13.9, 95% CI = 7.4-21.1, p < 0.0001), pre-term delivery (<32 weeks) (RR = 12.0, 95% CI = 4.9-21.6, p < 0.0001), pre-eclampsia (RR = 4.0, 95% CI = 1.6-7.4, p = 0.006), and decreased fetal movement (RR = 3.3, 95% CI = 1.6-5.2, p = 0.0018). Abnormal placental development is an underlying mechanism that may explain the constellation of observed complications in our study. Thus, we hypothesize that TTD DNA repair and transcription genes play an important role in normal human placental development.
R Moslehi; C Signore; D Tamura; J L Mills; J J Digiovanna; M A Tucker; J Troendle; T Ueda; J Boyle; S G Khan; K-S Oh; A M Goldstein; K H Kraemer
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2009-12-10
Journal Detail:
Title:  Clinical genetics     Volume:  77     ISSN:  1399-0004     ISO Abbreviation:  Clin. Genet.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-05-07     Completed Date:  2010-09-14     Revised Date:  2013-03-27    
Medline Journal Info:
Nlm Unique ID:  0253664     Medline TA:  Clin Genet     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  365-73     Citation Subset:  IM    
Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
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MeSH Terms
DNA Repair / genetics*
Fetal Development / genetics*
Live Birth
Middle Aged
Pregnancy Outcome
Reference Values
Transcription, Genetic*
Trichothiodystrophy Syndromes / embryology*,  genetics*
Young Adult
Grant Support

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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