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Study of the Genetic and Epigenetic Causes of Recurrent Hydatidiform Moles

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01008501
Recruitment Status : Recruiting
First Posted : November 5, 2009
Last Update Posted : March 5, 2021
Information provided by (Responsible Party):
Ignatia Van den Veyver, Baylor College of Medicine

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.

Condition or disease
Hydatidiform 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 and/or 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.

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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: Genetic Studies in Gestational Trophoblastic Disease
Actual Study Start Date : December 1998
Estimated Primary Completion Date : January 2025
Estimated Study Completion Date : January 2025

Individuals with recurrent or sporadic hydatidiform moles and their first-degree family members. Sometimes additional family members are also enrolled.

Biospecimen Retention:   Samples With DNA
lymphoblast DNA; tissue

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Individuals who have had sporadic or recurrent hydatidiform moles and their first degree relatives. Sometimes additional family members are also enrolled.

Inclusion Criteria:

  • Personal or family history of recurrent moles or a sporadic mole
  • Presence of a mutation in NLRP7

Exclusion Criteria:

  • None

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01008501

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Contact: Ignatia Van den Veyver, MD 832-824-8125
Contact: Renee Elawar 832-824-8156

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United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Ignatia B Van den Veyver, MD    713-798-4914   
Principal Investigator: Ignatia B Van den Veyver, MD         
Sponsors and Collaborators
Baylor College of Medicine
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Principal Investigator: Ignatia B Van den Veyver, MD Baylor College of Medicine
Publications of Results:

Other Publications:

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Responsible Party: Ignatia Van den Veyver, Professor, Baylor College of Medicine Identifier: NCT01008501    
Other Study ID Numbers: BCM Hydatidiform Mole H7345
First Posted: November 5, 2009    Key Record Dates
Last Update Posted: March 5, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Patient data with no identification information will be published following peer review in journals and/or presented at scientific meetings.
Keywords provided by Ignatia Van den Veyver, Baylor College of Medicine:
hydatidiform moles
complete hydatidiform moles
partial hydatidiform moles
Molar pregnancy
pregnancy wastage
sporadic hydatidiform moles
recurrent hydatidiform moles
Additional relevant MeSH terms:
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Hydatidiform Mole
Gestational Trophoblastic Disease
Trophoblastic Neoplasms
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Pregnancy Complications, Neoplastic
Pregnancy Complications