Mosaic moles and non-familial biparental moles are not caused by mutations in NLRP7, NLRP2 or C6orf221

Andreasen, Lotte; Bolund, Lars; Niemann, Isa; Hansen, Estrid Stæhr; Sunde, Lone

doi:10.1093/molehr/gas036

Cited by 10 publications

(11 citation statements)

References 33 publications

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“…Mutations in KHDC3 were found in women with familial diploid biparental hydatidiform mole s from four families [ 47 , 48 ] and in two unrelated women with diploid biparental hydatidiform mole s but without familial hydatidiform mole s [ 49 ]. However, discordant evidence seems to exclude mutations in this gene as a cause of non-familial biparental moles [ 50 ] and androgenetic moles [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Expression of maternally derived KHDC3, NLRP5, OOEP and TLE6is associated with oocyte developmental competence in the ovine species

et al. 2014

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BackgroundThe sub-cortical maternal complex (SCMC), located in the subcortex of mouse oocytes and preimplantation embryos, is composed of at least four proteins encoded by maternal effect genes: OOEP, NLRP5/MATER, TLE6 and KHDC3/FILIA. The SCMC assembles during oocyte growth and was seen to be essential for murine zygote progression beyond the first embryonic cell divisions; although roles in chromatin reprogramming and embryonic genome activation were hypothesized, the full range of functions of the complex in preimplantation development remains largely unknown.ResultsHere we report the expression of the SCMC genes in ovine oocytes and pre-implantation embryos, describing for the first time its expression in a large mammalian species.We report sheep-specific patterns of expression and a relationship with the oocyte developmental potential in terms of delayed degradation of maternal SCMC transcripts in pre-implantation embryos derived from developmentally incompetent oocytes.In addition, by determining OOEP full length cDNA by Rapid Amplification of cDNA Ends (RACE) we identified two different transcript variants (OOEP1 and OOEP2), both expressed in oocytes and early embryos, but with different somatic tissue distributions.In silico translation showed that 140 aminoacid peptide OOEP1 shares an identity with orthologous proteins ranging from 95% with the bovine to 45% with mouse. Conversely, OOEP2 contains a premature termination codon, thus representing an alternative noncoding transcript and supporting the existence of aberrant splicing during ovine oogenesis.ConclusionsThese findings confirm the existence of the SCMC in sheep and its key role for the oocyte developmental potential, deepening our understanding on the molecular differences underlying cytoplasmic vs nuclear maturation of the oocytes.Describing differences and overlaps in transcriptome composition between model organisms advance our comprehension of the diversity/uniformity between mammalian species during early embryonic development and provide information on genes that play important regulatory roles in fertility in nonmurine models, including the human.Electronic supplementary materialThe online version of this article (doi:10.1186/s12861-014-0040-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Expression of maternally derived KHDC3, NLRP5, OOEP and TLE6is associated with oocyte developmental competence in the ovine species

et al. 2014

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“…Other studies have also not been able to confirm the previously suggested association between mutations in NLRP7 and androgenetic or diandric triploid forms of HM, providing additional indication that BiHM have different origins than AnCHM and diandric triploid PHM. 14,21 The evolving lack of support for the involvement of these genes in adverse reproductive outcomes other than BiHM has important implications for clinical diagnostic testing for mutations in these genes, which may only be indicated in the presence of proven BiHM or highly recurrent HM (more than two) of unknown inheritance and genotype. Because most of these studies were carried out in relatively small cohorts, larger multicenter collaborative studies may be required to conclusively demonstrate that mutations in NLRP7 or KHDC3L in women are uniquely responsible for recurrent rare BiHM.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2013

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Objective: 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 biparental hydatidiform moles. Method: We recruited 16 women with suspected recurrent and sporadic AnCHM and 5 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 SNPs in patients with AnCHM. However in patients with BiHM, we identified a novel homozygous mutation and a previously described intragenic duplication of exon 2-5 in NLRP7, both of which are likely to be disease causing. We did not identify mutations in KHDC3L in patients with the either forms of HM. Conclusions: The absence of mutations in the women with AnCHM supports a role of 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 to NLRP7, the major BiHM gene.

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“… 12 One of these 3 cases (case 131) was part of an extensively studied family in which the mother carries mutations in both alleles of NLRP7 . 5 , 22 – 24 …”

Section: Methodsmentioning

confidence: 99%

Paternal Hemizygosity in 11p15 in Mole-like Conceptuses

et al. 2015

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Hydatidiform mole is an abnormal human pregnancy characterized by the fetus being absent or nonviable, and the chorionic villi being vesicular and with trophoblastic hyperplasia. Most often, the mole phenotype is seen in conceptuses with an excess of paternally inherited genome set(s) relative to maternally inherited genome set(s), suggesting that the phenotype is caused by an excess of genome with a paternal imprinting pattern. However, it is unknown if correct parental origin of every imprinted gene is crucial for normal early differentiation or if abnormal parental imprinting of only one, or some, gene(s) can cause the mole phenotype.Two conceptuses included in the Danish Mole Project stood out since they presented with vesicular chorionic villi and without signs of fetal differentiation, and had apparently biparental diploid genomes, and no mutations in NLRP7 or KHDC3L were detected in the mothers. These conceptuses were subjected to a centralized histopathological revision and their genetic complements were scrutinized using fluorescence in situ hybridization, and DNA-marker and array comparative genomic hybridization analyses. Both conceptuses showed dysmorphic chorionic villi with some similarities to hydatidiform moles; however, no definite florid trophoblast hyperplasia was observed. Both conceptuses showed paternal hemizygosity of 11pter-11p15.4, most likely in nonmosaic state.Our findings suggest that the product of one (or a few) maternally expressed gene(s) on the tip of chromosome 11 is necessary for normal early embryonic differentiation. However, since the present two cases did not exhibit all features of hydatidiform moles, it is likely that abnormal parental imprinting of genes in other regions contribute to the phenotype of a hydatidiform mole.

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Mosaic moles and non-familial biparental moles are not caused by mutations in NLRP7, NLRP2 or C6orf221

Cited by 10 publications

References 33 publications

Expression of maternally derived KHDC3, NLRP5, OOEP and TLE6is associated with oocyte developmental competence in the ovine species

Expression of maternally derived KHDC3, NLRP5, OOEP and TLE6is associated with oocyte developmental competence in the ovine species

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

Paternal Hemizygosity in 11p15 in Mole-like Conceptuses

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