Recurrent complete hydatidiform mole: where we are, is there a safe gestational horizon? Opinion and mini-review

Kalogiannidis, Ioannis; Kalinderi, Kallirhoe; Kalinderis, Michail; Miliaras, Dimosthenis; Tarlatzis, Basil C.; Athanasiadis, Apostolos

doi:10.1007/s10815-018-1202-9

Cited by 36 publications

(27 citation statements)

References 30 publications

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“…This suggests that it may coordinate cytokines secretion and transportation (Messaed et al 2011). In addition, NLRP7 is referred to as a maternal-effect gene, whose mutations commonly result in recurrent hydatidiform moles (RHMs), a gestational trophoblastic disease characterized by a mass exhibiting trophoblastic hyperplasia and swelling of chorionic villi as well as impaired embryonic development (Murdoch et al 2006, Sebire et al 2013, Nguyen et al 2014, Carey et al 2015, Ito et al 2016, Sills et al 2017, Kalogiannidis et al 2018). The homozygous or compound heterozygous NLRP7 missense and non-sense mutations in male do not jeopardize their normal reproductive outcomes and this indicates that NLRP7 may specifically regulate female reproduction (Qian et al 2007, Wang et al 2009).…”

Section: Introductionmentioning

confidence: 99%

NLRP7 is expressed in the ovine ovary and associated with in vitro pre-implantation embryo development

Tian

Zhang

et al. 2019

Reproduction

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NLRP (NACHT, LRR and PYD domain-containing proteins) family plays pivotal roles in mammalian reproduction. Mutation of NLRP7 is often associated with human recurrent hydatidiform moles. Few studies regarding the functions of NLRP7 have been performed in other mammalian species rather than humans. In the current study, for the first time, the function of NLRP7 has been explored in ovine ovary. NLRP7 protein was mainly located in ovarian follicles and in in vitro pre-implantation embryos. To identify its origin, 763 bp partial CDS of NLRP7 deriving from sheep cumulus oocyte complexes (COCs) was cloned, it showed a great homology with Homo sapiens. The high levels of mRNA and protein of NLRP7 were steadily expressed in oocytes, parthenogenetic embryos or IVF embryos. NLRP7 knockdown by the combination of siRNA and shRNA jeopardized both the parthenogenetic and IVF embryo development. These results strongly suggest that NLRP7 plays an important role in ovine reproduction. The potential mechanisms of NLRP7 will be fully investigated in the future.

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Section: Introductionmentioning

confidence: 99%

NLRP7 is expressed in the ovine ovary and associated with in vitro pre-implantation embryo development

Tian

Zhang

et al. 2019

Reproduction

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“…Compared to POC results of another group [12], the prevalence of wgUPD in our study was similar (0.47% vs. 0.5%), but the prevalence of triploidy in our study was lower (3.9% vs. 6.3%). Aside from the rare recurrent CHM with a biparental diploid karyotype, which is an autosomal recessive disease called familial recurrent HM (FRHM) due to biallelic mutations in 2 genes: NLRP7 at 19q13.42 [15] [16], and more rarely, KHDC3L at 6q13 [17], the genetic abnormalities associated with cases of triploidy with PHM, and the wgUPD associated with CHM can be reliably detected by oligo-SNP based CMA; correlation with clinical findings, histopathological features, p57 (KIP2) immunohistochemistry, and genotyping results may ensure accurate classification in equivocal cases [14].…”

Section: Discussionmentioning

confidence: 99%

Single Nucleotide Polymorphism-Based Chromosomal Microarray Evaluation of Hydatidiform Moles: A US National Reference Laboratory Experience

Anguiano¹,

Wang²,

Lammers³

et al. 2020

OJOG

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Objectives: This retrospective study evaluated 1) benefits of single nucleotide polymorphism (SNP)-based chromosomal microarrays (CMAs) in the diagnosis of complete hydatidiform mole (CHM) and partial HM (PHM) in products of conception (POC) and amniotic fluid (AF) specimens, and 2) frequency of whole-genome uniparental disomy (wgUPD) and triploidy in POC and AF specimens received at a US national reference laboratory. Methods: We reviewed consecutive 2138 POC and 3230 AF specimens and identified the cases with wgUPD and triploidy which are associated with molar pregnancy. Results: Of 2138 consecutive POC specimens tested, SNP-based CMA detected wgUPD in 10 (0.47%) and triploidy in 84 (3.93%). Of the 10 wgUPD cases, 9 (90%) were confirmed as CHM. Of 3230 consecutive AF specimens, the array detected wgUPD in 1 case (0.03%) and triploidy in 11 (0.34%). Conclusions: SNP-based microarray allows detection of wgUPD in POC and AF specimens at a US national reference laboratory. Correctly diagnosing HM and differentiating CHM from PHM are important for clinical management. The effective SNP-based CMA detection of wgUPD in CHM may enable physicians to monitor patients at risk for gestational trophoblastic disease and neoplasm. Conventional chromosome analysis of POC has a high failure rate, cannot be performed on formalin-fixed paraffin embedded samples, and cannot detect wgUPD. Further multi-institutional collaborative assessment

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“…In 2011, a pioneer study reported for the first time that biallelic KHDC3L mutations caused the familial complete hydatidiform mole [31], an extreme infertility condition that is characterized by early embryonic arrest and excessive trophoblastic proliferation. The observed phenotype was attributed to abnormal maternal gene imprinting [71,72]. Follow-up studies also identified several other biallelic mutations of KHDC3L that are causal to complete hydatidiform mole [68,73].…”

Section: Discussionmentioning

confidence: 99%

KHDC3L mutation causes recurrent pregnancy loss by inducing genomic instability of human early embryonic cells

et al. 2019

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Recurrent pregnancy loss (RPL) is an important complication in reproductive health. About 50% of RPL cases are unexplained, and understanding the genetic basis is essential for its diagnosis and prognosis. Herein, we report causal KH domain containing 3 like (KHDC3L) mutations in RPL. KHDC3L is expressed in human epiblast cells and ensures their genome stability and viability. Mechanistically, KHDC3L binds to poly(ADP-ribose) polymerase 1 (PARP1) to stimulate its activity. In response to DNA damage, KHDC3L also localizes to DNA damage sites and facilitates homologous recombination (HR)-mediated DNA repair. KHDC3L dysfunction causes PARP1 inhibition and HR repair deficiency, which is synthetically lethal. Notably, we identified two critical residues, Thr145 and Thr156, whose phosphorylation by Ataxia-telangiectasia mutated (ATM) is essential for KHDC3L’s functions. Importantly, two deletions of KHDC3L (p.E150_V160del and p.E150_V172del) were detected in female RPL patients, both of which harbor a common loss of Thr156 and are impaired in PARP1 activation and HR repair. In summary, our study reveals both KHDC3L as a new RPL risk gene and its critical function in DNA damage repair pathways.

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Recurrent complete hydatidiform mole: where we are, is there a safe gestational horizon? Opinion and mini-review

Cited by 36 publications

References 30 publications

NLRP7 is expressed in the ovine ovary and associated with in vitro pre-implantation embryo development

NLRP7 is expressed in the ovine ovary and associated with in vitro pre-implantation embryo development

Single Nucleotide Polymorphism-Based Chromosomal Microarray Evaluation of Hydatidiform Moles: A US National Reference Laboratory Experience

KHDC3L mutation causes recurrent pregnancy loss by inducing genomic instability of human early embryonic cells

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