Ignite Creation Date:
2024-05-05 @ 9:59 PM
Last Modification Date:
2024-10-26 @ 10:12 AM
Study NCT ID:
NCT01008501
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-10-30
First Post:
2009-11-04
Brief Title:
Study of the Genetic and Epigenetic Causes of Recurrent Hydatidiform Moles
Sponsor:
Baylor College of Medicine
Organization:
Baylor College of Medicine
Study Overview
Official Title:
Genetic Studies in Gestational Trophoblastic Disease
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2023-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The researchers laboratory is studying a rare class of highly recurrent hydatidiform moles These are usually complete hydatidiform moles CHM but sometimes they are partial hydatidiform moles PHM With sporadic moles the difference between CHMs and PHMs is that with CHMS there is not typically an embryo or fetus at the time of diagnosis but with a PHM there may be a fetus Also CHMs have 46 chromosomes in each cell While this is the number of chromosomes that should be found the problem is that all the chromosomes come from the father Normally half the chromosomes should come from the mother and half should come from the father Unlike CHMs PHMs have 69 chromosomes This means that PHMs have three copies of each chromosome when they should only have two The extra copy comes from the father
The researchers study focuses on moles that are genetically different from these sporadic moles in that they have 23 chromosomes from the mother and 23 chromosomes from the father - just like a normally developing pregnancy These are called biparental moles because the mutation that causes the mole comes from both parents This mutation occurs in a gene called NLRP7 The researchers team is working to understand how mutations in NLRP7 leads to CHMs and how these mutations may lead to other types of pregnancy loss The researchers are also trying to discover other genetic and epigenetic factors that may lead to moles
The researchers study focuses on moles that are genetically different from these sporadic moles in that they have 23 chromosomes from the mother and 23 chromosomes from the father - just like a normally developing pregnancy These are called biparental moles because the mutation that causes the mole comes from both parents This mutation occurs in a gene called NLRP7 The researchers team is working to understand how mutations in NLRP7 leads to CHMs and how these mutations may lead to other types of pregnancy loss The researchers are also trying to discover other genetic and epigenetic factors that may lead to moles
Detailed Description:
Hydatidiform mole HM is the product of an aberrant human pregnancy in which there is abnormal embryonic development and abnormal proliferation of placental villi The incidence of HM varies between ethnic groups and occurs in 1 in every 1500 pregnancies in the USA All HM cases are sporadic except for extremely rare familial cases The exact mechanisms leading to molar pregnancies are not known Hydatidiform moles are classified based on histology and karyotype data into two types
complete hydatidiform moles CHM and partial hydatidiform moles PHM The complete forms are characterized by general trophoblastic proliferation and absence of an embryo and amniotic membranes In most of the cases CHM have a diploid genome and are androgenetic with two identical sets of paternal chromosomes Partial hydatidiform moles are characterized by focal trophoblastic proliferation Embryos and amniotic membranes are usually present in these molar pregnancies Partial hydatidiform moles are mostly triploid with two sets of paternal chromosomes and one set of maternal chromosomes The comparison of findings in androgenetic CHM and PHM indicate that both maternally under expressed and paternally over expressed genes play a role in the pathophysiology of molar pregnancies Very few genetic studies have been performed on molar pregnancies or the patients who carry these pregnancies A few studies have looked at the over- or underexpression of genes that may play a role in the progression or invasiveness of hydatidiform moles however none have addressed the underlying genetic etiology We have been able to study an inbred family of which several female members have had recurrent hydatidiform moles and have now genetically mapped the defective gene responsible for the molar pregnancies in this family We then worked towards refined characterization of the genetic locus containing the mutated gene and analysis of candidate genes in this region for mutations leading to molar pregnancy Because the hydatidiform moles in these patients have abnormal genetic imprinting we believe that this candidate gene is important for establishment of genetic imprinting in the maternal germline Recently another group of investigators studying this condition identified mutations in a gene NALP7 now renamed to NLRP7 in some of the affected women We confirmed this in other subjects studied by us This is the first identified gene but there is genetic heterogeneity and other genes still remain to be found In addition the normal function of this gene in reproduction and how it leads to recurrent moles when mutated remains to be determined To study both of these it will be very important to collect as many molar pregnancy tissue samples as possible as well as blood samples andor other non-invasively obtained samples such as buccal swabs and saliva from affected patients and their families Recent evidence suggests that mutations in NLRP7 might cause other forms of reproductive failure such as triploid spontaneous abortions It has further been proposed that the mutation status of NLRP7 in women with recurrent reproductive loss is an important predictor of the outcome of Assisted Reproductive Technologies Therefore we are carrying out mutation analysis of NLRP2 and NLRP7 in women with unexplained infertility and other forms of reproductive failure
complete hydatidiform moles CHM and partial hydatidiform moles PHM The complete forms are characterized by general trophoblastic proliferation and absence of an embryo and amniotic membranes In most of the cases CHM have a diploid genome and are androgenetic with two identical sets of paternal chromosomes Partial hydatidiform moles are characterized by focal trophoblastic proliferation Embryos and amniotic membranes are usually present in these molar pregnancies Partial hydatidiform moles are mostly triploid with two sets of paternal chromosomes and one set of maternal chromosomes The comparison of findings in androgenetic CHM and PHM indicate that both maternally under expressed and paternally over expressed genes play a role in the pathophysiology of molar pregnancies Very few genetic studies have been performed on molar pregnancies or the patients who carry these pregnancies A few studies have looked at the over- or underexpression of genes that may play a role in the progression or invasiveness of hydatidiform moles however none have addressed the underlying genetic etiology We have been able to study an inbred family of which several female members have had recurrent hydatidiform moles and have now genetically mapped the defective gene responsible for the molar pregnancies in this family We then worked towards refined characterization of the genetic locus containing the mutated gene and analysis of candidate genes in this region for mutations leading to molar pregnancy Because the hydatidiform moles in these patients have abnormal genetic imprinting we believe that this candidate gene is important for establishment of genetic imprinting in the maternal germline Recently another group of investigators studying this condition identified mutations in a gene NALP7 now renamed to NLRP7 in some of the affected women We confirmed this in other subjects studied by us This is the first identified gene but there is genetic heterogeneity and other genes still remain to be found In addition the normal function of this gene in reproduction and how it leads to recurrent moles when mutated remains to be determined To study both of these it will be very important to collect as many molar pregnancy tissue samples as possible as well as blood samples andor other non-invasively obtained samples such as buccal swabs and saliva from affected patients and their families Recent evidence suggests that mutations in NLRP7 might cause other forms of reproductive failure such as triploid spontaneous abortions It has further been proposed that the mutation status of NLRP7 in women with recurrent reproductive loss is an important predictor of the outcome of Assisted Reproductive Technologies Therefore we are carrying out mutation analysis of NLRP2 and NLRP7 in women with unexplained infertility and other forms of reproductive failure
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None