title: Effect of mutations in XPD(ERCC2) on pregnancy and prenatal development in mothers of patients with trichothiodystrophy or xeroderma pigmentosum.
abstract: The XPD(ERCC2) gene encodes a DNA helicase involved in DNA repair and transcription. Patients with mutations in XPD may have different autosomal recessive phenotypes including trichothiodystrophy (TTD) or xeroderma pigmentosum (XP). TTD patients have sulfur-deficient, brittle hair, short stature and developmental delay. In contrast, XP patients have freckle-like pigmentation and a greatly increased risk of sun-induced skin cancers. Mothers of TTD patients have been reported to have a high frequency of pregnancy and neonatal complications. We performed a molecular epidemiological study of 15 mothers of 17 TTD patients and 13 mothers of 17 XP patients, all with XPD mutations. We found that 94% (16/17) of the TTD pregnancies had pre-term delivery, pre-eclampsia, hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, prematurity or low birth weight. None of the 17 XP pregnancies had these complications (P<0.001). As mutations in XPD may have differential effects on DNA repair and transcription, these observations should provide insights into the role of XPD in human pregnancy and fetal development.
authors.affiliation: Dermatology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-4258, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Tamura
authors.forename: Sikandar G
authors.initials: SG
authors.lastname: Khan
authors.forename: Melissa
authors.initials: M
authors.lastname: Merideth
authors.forename: John J
authors.initials: JJ
authors.lastname: DiGiovanna
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Tucker
authors.forename: Alisa M
authors.initials: AM
authors.lastname: Goldstein
authors.forename: Kyu-Seon
authors.initials: KS
authors.lastname: Oh
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ueda
authors.forename: Jennifer
authors.initials: J
authors.lastname: Boyle
authors.forename: Mansi
authors.initials: M
authors.lastname: Sarihan
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Kraemer
mesh_terms: D005260:Female; D047109:Fetal Development / Q000235:genetics*; D005315:Fetal Diseases / Q000175:diagnosis / Q000235:genetics; D017359:HELLP Syndrome / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D011225:Pre-Eclampsia / Q000175:diagnosis / Q000235:genetics; D011247:Pregnancy; D047928:Premature Birth; D054463:Trichothiodystrophy Syndromes / Q000150:complications / Q000235:genetics*; D014983:Xeroderma Pigmentosum / Q000175:diagnosis / Q000235:genetics*; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human