EPOXIDE HYDROLASE AND PHENYTOIN INDUCED TERATOGENESIS
EPOXIDE HYDROLASE AND PHENYTOIN INDUCED TERATOGENESIS
批准号:
6176087
负责人:
LAURENCE E WALSH
金额:
$4.63万
依托单位国家:
美国
项目类别:
财政年份:
2000
资助国家:
美国
项目状态:
未结题
起止时间:
2000-07-01 至
关键词:
child (0-11) cleft lip cleft palate clinical research congenital heart disorder cytogenetics embryo /fetus drug adverse effect enzyme activity epoxide hydrolase family genetics gene expression genetic polymorphism genetically modified animals genotype human genetic material tag human subject laboratory mouse leukocytes nucleic acid sequence phenotype phenytoin polymerase chain reaction siblings single strand conformation polymorphism teratogens
中文摘要
胎儿苯妥英综合征(FHS)是一种与苯妥英相关的畸形
英文摘要
Fetal hydantoin syndrome (FHS) is a phenytoin-related malformation
syndrome characterized by craniofacial anomalies, limb dysmorphisms, and
often central nervous system involvement. The syndrome may be associated
with genetic polymorphisms or mutations causing variability in
xenobiotic microsomal epoxide hydrolase (mEH), an enzyme responsible for
detoxification of the arene oxide metabolite of phenytoin (Dilantin).
In this Individual National Research Training Award application, the
applicant proposes to test this hypothesis pursuing the aims and methods
discussed below.
The applicant will obtain blood samples from individuals who fulfill
diagnostic criteria for fetal hydantoin syndrome (FHS), fetal hydantoin
effect (FHE), or who have oral clefting, congenital heart disease, or
other major malformations associated with history of first trimester in
utero phenytoin exposure, and have similarly exposed, but unaffected,
siblings to be used as controls. After isolating leukocytes, he will
use the sponsor's standard enzyme-indicator assay and high performance
liquid chromatography (HPLC) to determine leukocyte mEH activity in
affected and unaffected siblings, and evaluate these data for a
significant difference between two groups. He will then determine the
nature and incidence of mEH DNA sequence polymorphisms by isolating
subjects genomic DNA, amplifying the mEH exons using polymerase chain
reaction, screening for exon mutations via single-strand conformational
polymorphism (SSCP) analysis, distinguishing alleles using allele-
specific oligonucleotide (ASO) hybridization and an allele-specific
restriction enzyme digest, and sequencing of candidate fragments. As
permitted by projected duration of support, the applicant will also
begin application of in vitro expression systems and transgenic animals
to characterization of mEH genotypic variability and its subsequent
phenotypes. Completion of this proposal will facilitate the applicant
s training in molecular biology and medical genetics, and will
contribute to the understanding of phenytoin-induced embryopathy as well
as,
possibly, teratogenesis associated with other related agents.
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
Inherited epilepsies.
遗传性癫痫。
DOI:
10.1053/spen.2001.26450
发表时间:
2001
期刊:
Seminars in pediatric neurology.
影响因子:
--
作者:
[Walsh,LE, McCandless,D]
通讯作者:
McCandless,D
EPOXIDE HYDROLASE AND PHENYTOIN INDUCED TERATOGENESIS
-
批准号:6088496
-
项目类别:
-
资助金额:$4.53万
-
财政年份:2001
-
负责人:LAURENCE E WALSH
-
依托单位:
EPOXIDE HYDROLASE AND PHENYTOIN INDUCED TERATOGENESIS
-
批准号:2639725
-
项目类别:
-
资助金额:$3.7万
-
财政年份:1998
-
负责人:LAURENCE E WALSH
-
依托单位:
海外基金