Skip to main content
ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #307763
Title: No evidence for mutations in NLRP7 and KHDC3L in women with androgenetic hydatidiform moles

Author
item MAHADEVAN, SANGEETHA - Baylor College Of Medicine
item WEN, SHU - Baylor College Of Medicine
item BALASA, ALFRED - Children'S Nutrition Research Center (CNRC)
item FRUHMAN, GARY - Baylor College Of Medicine
item MATEUS, JULIO - University Of Texas Medical Branch
item WAGNER, ANDREW - University Of Oklahoma
item AL-HUSSAINI, TAREK - Assiut University
item VAN DEN VEYVER, IGNATIA - Children'S Nutrition Research Center (CNRC)

Submitted to: Prenatal Diagnosis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/4/2013
Publication Date: 12/10/2013
Citation: Mahadevan, S., Wen, S., Balasa, A., Fruhman, G., Mateus, J., Wagner, A., Al-Hussaini, T., Van Den Veyver, I.B. 2013. No evidence for mutations in NLRP7 and KHDC3L in women with androgenetic hydatidiform moles. Prenatal Diagnosis. 33(13):1242-1247.

Interpretive Summary: Biparental Hydatidiform Mole (BiHM) is a rare pregnancy complication in which the placenta (afterbirth) becomes abnormally developed and fills with fluid, but cannot sustain growth and development of a fetus. The disease can be caused by loss of the function of one of two genes, NLRP7 and KHDC3L in pregnant women, which results in abnormal DNA methylation (change of DNA that helps regulate turning on/off of genes at the right time and tissue) in the placenta. It is known that DNA methylation is important in normal function of the placenta, which is the main organ supplying the fetus with nutrients. To understand the role of NLRP7 and KHDC3L in normal function of the placenta, in this study we looked at whether losing function of these genes could also cause other types of hydatidifom moles. We could not confirm this and found that they only cause the BiHM type. While this study does not investigate nutrition-related functions of the placenta itself, it is a component of our work on understanding how genes in the placenta are regulated by DNA methylation. This is important for understanding how the placenta controls fetal nutrition.

Technical Abstract: The objective of this study was to evaluate the mutational spectrum of NLRP7 and KHDC3L (C6orf221) in women with sporadic and recurrent androgenetic complete hydatidiform moles (AnCHM) and biparental hydatidiform moles (BiHM) to address the hypothesis that autosomal recessive mutations in these genes are only or primarily associated with BiHM. We recruited 16 women with suspected recurrent and sporadic AnCHM and five women with suspected BiHM in addition to their reproductive partners into our study. We then sequenced the coding exons of NLRP7 and KHDC3L from DNA isolated from either blood or saliva from the study subjects. Sequence analysis of NLRP7 and KHDC3L revealed previously described single nucleotide polymorphisms in patients with AnCHM. However, in patients with BiHM, we identified a novel homozygous mutation and a previously described intragenic duplication of exons 2 to 5 in NLRP7, both of which are likely to be disease causing. We did not identify mutations in KHDC3L in patients with either form of hydatidiform moles. The absence of mutations in women with AnCHM supports a role for NLRP7 or KHDC3L in BiHM only. The absence of mutations in KHDC3L in women with BiHM is consistent with its minor role in this disease compared with NLRP7, the major BiHM gene.