A novel NLRP7 protein-truncating mutation associated with discordant and divergent p57 immunostaining in diploid biparental and triploid digynic moles

Allias, Fabienne; Mechtouf, Nawel; Gaillot-Durand, Lucie; Hoffner, Lori; Hajri, Touria; Devouassoux‐Shisheboran, Mojgan; Massardier, Jérôme; Golfier, François; Bolze, Pierre‐Adrien; Surti, Urvashi; Slim, Rima

doi:10.1007/s00428-020-02769-w

Cited by 11 publications

(8 citation statements)

References 17 publications

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“…Loss of appropriate imprinting results in a molar phenotype for any products of conception (POC) in affected women including normal biparental conceptions and digynic triploids [31,32], genotypes not normally associated with HM.…”

Section: (Iii) Genomic Imprinting In Hydatidiform Molesmentioning

confidence: 99%

Genetics of gestational trophoblastic disease

Fisher

Maher

2021

Best Practice & Research Clinical Obstetrics & Gynaecol

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Section: (Iii) Genomic Imprinting In Hydatidiform Molesmentioning

confidence: 99%

Genetics of gestational trophoblastic disease

Fisher

Maher

2021

Best Practice & Research Clinical Obstetrics & Gynaecol

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“…[22][23][24][25] Majority of these mutations (>60%) were protein truncating (nonsense, frameshift, or splice site) followed by missense mutations that were found in around 30-35% of cases. 14,[23][24][25] The c.2655dupC (p.Ile886HisfsTer11) variant found in our case is located in the C-terminal LRR domain of the gene, which harbors majority of reported mutation. In contrast, the missense variant found in our patient (c.1358T > G, p.Ile453Ser) is located in the NACHT domain of the gene.…”

Section: Discussionmentioning

confidence: 99%

Two Novel Variants in NLRP7 Gene in an Egyptian Female Patient with Consecutive Molar Pregnancies Complicated by Choriocarcinoma

Shalabi¹,

Abdel‐Hamid²,

Shaker³

2019

International Journal of Infertility &Amp; Fetal Medicine

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Background: Hydatidiform mole, whether complete or partial mole, is one of the most common forms of gestational trophoblastic disease. It is characterized by extreme trophoblastic proliferation and atypical embryonic growth. Though almost all of complete hydatidiform moles are diploid androgenetic, scarce cases are biparental and caused mainly by mutations in NLRP7 and KHDC3L genes. NLRP7 mutations are more common and were reported in around 50-80% of cases from diverse populations while KHDC3 mutations were only found in 5-10% of cases. Case description: A healthy 40-year-old Egyptian woman was referred to the Clinic of Prenatal Diagnosis and Fetal Medicine Department for counseling. She was married for 20 years to a first-degree relative and experienced 17 consecutive pregnancy losses without having any live births. Uterus ultrasound revealed endometrial thickening and subseptate uterus and in her last pregnancy failure, she complained of abdominal pain and severe shortness of breath. Immunochemistry tests were positive for β-human chorionic gonadotropin and histopathology-confirmed choriocarcinoma. Genetic testing revealed two novel heterozygous variants in the NLPR7 gene. Conclusion: We presented a case with 17 recurrent hydatidiform moles that was complicated by choriocarcinoma due to novel variants in the NLRP7 gene. Clinical significance: This is the first Egyptian case with recurrent hydatidiform mole. We identified novel NLPR7 variants, thus expanding the mutational spectrum associated with this rare disease.

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“…In one of these two HM tissues, the triploid digynic genotype was found to have resulted from the failure of the extrusion of the second polar body during meiosis II (Allias et al, 2020). Data on these two triploid digynic HMs demonstrated, therefore, another meiotic abnormality, that can occur, although rarely, in the oocytes of patients with biallelic NLRP7 variants.…”

Section: Hms From Patients With Biallelic Nlrp7 Pathogenic or Likely ...mentioning

confidence: 92%

“…However, this tissue was genotyped at only two loci, and consequently, its genotype is not convincing (Ulker et al, 2013). The remaining two HM tissues were analyzed at several STR, were welldocumented to be triploid digynic (Allias et al, 2020;Fallahian et al, 2013), and are indicated by asterisks above their associated variants in Figure 2.…”

Section: Hms From Patients With Biallelic Nlrp7 Pathogenic or Likely ...mentioning

confidence: 99%

Biallelic NLRP7 variants in patients with recurrent hydatidiform mole: A review and expert consensus

et al. 2022

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Hydatidiform mole (HM) is an abnormal human pregnancy characterized by excessive growth of placental trophoblasts and abnormal early embryonic development. Following a first such abnormal pregnancy, the risk for women of successive molar pregnancies significantly increases. To date variants in seven maternal-effect genes have been shown to cause recurrent HMs (RHM). NLRP7 is the major causative gene for RHM and codes for NOD-like receptor (NLR) family pyrin domain containing 7, which belongs to a family of proteins involved in inflammatory disorders. Since its identification, all NLRP7 variants have been recorded in Infevers, an online registry dedicated to autoinflammatory diseases (https://infevers.umaimontpellier.fr/web/). Here, we reviewed published and unpublished recessive NLRP7 variants associated with RHM, scored their pathogenicity according to the American College of Medical Genetics classification, and recapitulated all functional studies at the level of both the patients and the conceptions. We also provided data on further variant analyses of 32 patients and genotypes of 36 additional molar pregnancies. This comprehensive review integrates published and unpublished data on NLRP7 and aims at guiding geneticists and clinicians in variant interpretation, genetic counseling, and management of patients with this rare condition.

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A novel NLRP7 protein-truncating mutation associated with discordant and divergent p57 immunostaining in diploid biparental and triploid digynic moles

Cited by 11 publications

References 17 publications

Genetics of gestational trophoblastic disease

Genetics of gestational trophoblastic disease

Two Novel Variants in NLRP7 Gene in an Egyptian Female Patient with Consecutive Molar Pregnancies Complicated by Choriocarcinoma

Biallelic NLRP7 variants in patients with recurrent hydatidiform mole: A review and expert consensus

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