Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Dec;33(13):1242-7.
doi: 10.1002/pd.4239. Epub 2013 Oct 4.

No evidence for mutations in NLRP7 and KHDC3L in women with androgenetic hydatidiform moles

Sangeetha Mahadevan  1 , Shu Wen, Alfred Balasa, Gary Fruhman, Julio Mateus, Andrew Wagner, Tarek Al-Hussaini, Ignatia B Van den Veyver
Affiliations

No evidence for mutations in NLRP7 and KHDC3L in women with androgenetic hydatidiform moles

Sangeetha Mahadevan et al. Prenat Diagn. 2013 Dec.

Abstract

Objective: 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.

Method: 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.

Results: 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.

Conclusions: 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.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Tandem intragenic duplication of exons 2-5 of NLRP7 in women with recurrent BiHM
(A) A 32bp region of homology between intron 5 and intron 1 mediates recombination resulting in tandem duplication. (B) A PCR based strategy to detect the presence of the tandem duplication. A forward primer placed in intron 4 and reverse primer in intron 2 amplified a 1,221bp product in #8 (Lane 1), #14 (Lane 2) and #12 (Lane 3) but not in a control female (Lane 4).
Figure 2
Figure 2. A novel, damaging mutation in patient #14
A homozygous mutation in exon 5 of a patient (A, forward orientation) and (B, reverse orientation) with recurrent HM resulting in a C>T transition. This change was not seen in 200 control chromosomes (C and D). The c.1981C>T mutation changes a leucine to phenylalanine at amino acid position 661 in the NLRP7 transcript variant 3 which links the NAD and LRR domains (E). The leucine at this position in NLRP7 is conserved across primates and in the ancestral NLRP2 as well (F).
See this image and copyright information in PMC

References

    1. Judson H, Hayward BE, Sheridan E, et al. A global disorder of imprinting in the human female germ line. Nature. 2002 Apr 4;416(6880):539–42. PubMed PMID: 11932746. - PubMed
    1. Kou YC, Shao L, Peng HH, et al. A recurrent intragenic genomic duplication, other novel mutations in NLRP7 and imprinting defects in recurrent biparental hydatidiform moles. Mol Hum Reprod. 2008 Jan;14(1):33–40. PubMed PMID: 18039680. - PubMed
    1. Fisher RA, Hodges MD, Rees HC, et al. The maternally transcribed gene p57(KIP2) (CDNK1C) is abnormally expressed in both androgenetic and biparental complete hydatidiform moles. Hum Mol Genet. 2002 Dec 15;11(26):3267–72. PubMed PMID: 12471053. - PubMed
    1. Moglabey YB, Kircheisen R, Seoud M, et al. Genetic mapping of a maternal locus responsible for familial hydatidiform moles. Hum Mol Genet. 1999 Apr;8(4):667–71. PubMed PMID: 10072436. - PubMed
    1. Panichkul PC, Al-Hussaini TK, Sierra R, et al. Recurrent biparental hydatidiform mole: additional evidence for a 1.1-Mb locus in 19q13.4 and candidate gene analysis. J Soc Gynecol Investig. 2005 Jul;12(5):376–83. PubMed PMID: 15979551. - PubMed

Publication types