Contributions to the Genetics of Hydatidiform Moles and Fetal Loss
Yalcin Z, Gao Z, Abdelrazek IM, Bareke E, Majewski J, Abdalla E, Tan SL, Li L, Slim R. Two novel protein-truncating variants in NLRP2 and their functional impacts on the subcortical maternal complex. Clin Genet (2025 in press).
Slim R*. Genetics and Genomics of Gestational Trophoblastic Disease. Hematol Oncol Clin North Am. 38(6):1219-1232, 2024.
Rezaei M, Liang M, Yalcin Z, Martin JH, Kazami P, Bareke E, Ge ZJ, Fardaei M, Benadiva C, Hemida R, Hassan A, Maher G, Abdalla E, Buckett W, Bolze PA, Sandhu I, Duman O, Agrawal S, Qian J, Broojeni JV, Bhati L, Miron P, Allias F, Selim A, Fisher RA, Seckl M, Sauthier P, Touitou I, Tan SL, Majewski J, Taketo T, Slim R*. Meiosis I defects contribute to the genesis of androgenetic hydatidiform moles. J Clin Invest 134(22):e170669, 2024.
Liang M, Suresh B, Bareke E, Choufani S, Jagadeesh S, Weksberg R, Majewski J, Slim R*. A Homozygous Stop Codon in HORMAD2 in a Patient with Recurrent Digynic Triploid Miscarriage. Mol Genet Genomic Med. 2024 Feb;12(2):e2402. doi: 10.1002/mgg3.2402.
Yalcin Z, Liang M, Abdelrazek I, Friedrich C, Bareke E, Nabil A, Tüttelmann F, Majewski J, Abdalla E, Tan SL, Slim R*. A report of two homozygous TERB1 protein-truncating variants in two unrelated women with primary infertility. J Assist Reprod Genet. 2024 Jan 26. doi: 10.1007/s10815-024-03031-x. Online ahead of print.
Reynaud D, Alfaidy N, Collet C, Lemaitre N, Sergent F, Miege C, Soleilhac E, Al Assi A, Murthi P, Courtois G, Fauvarque MO, Slim R, Benharouga M, Abi Nahed R. NLRP7 Enhances Choriocarcinoma Cell Survival and Camouflage in an Inflammasome Independent Pathway, Cells 2023, 2023 Mar 9;12(6):857.
Slim R, Fisher R, Milhavet F, Hemida R, Rojas S, Rittore C, Bagga R, Aguinaga M, Touitou I. Biallelic NLRP7 variants in patients with recurrent hydatidiform mole: A review and expert consensus. Hum Mutat. Hum Mutat 2022 Dec;43(12):1732-1744. doi:10.1002/humu.24439. Epub 2022 Jul 23.
Finley J, Hay S , Oldzej J, Meredith MM, Dzidic N, Slim R, Aradhya S, HovanesK, Sahoo T. The genomic basis of sporadic and recurrent pregnancy loss: a comprehensive in-depth analysis of 24,900 miscarriages. Reprod Biomed Online, 2022 Jul;45(1):125-134. doi: 10.1016/j.rbmo.2022.03.014. Epub 2022 Mar 23.
Reynaud D, Abi Nahed R, Lemaitre N, Bolze PA, Traboulsi W, Sergent F, Battail C, Filhol O, Sapin V, Boufettal H, Hoffmann P, Aboussaouira T, Murthi P, Slim R, Benharouga M, Alfaidy N. (2021). NLRP7 Promotes ChoriocarcinomaGrowth and Progression through the Establishment of an Immunosuppressive Microenvironment. Cancers. 13(12): 2999
Rezaei M, Buckett W, Bareke E, Surti U, Majewski J, Slim R*. A protein-truncating mutation in CCNB3 in a patient with recurrent miscarriages and failure of meiosis I. J Med Genet. 2022 Jun;59(6):568-570. doi: 10.1136/jmedgenet-2021-107875. Epub 2021 May 21.
Martin JH, Slim R. (2021). Mono-pronuclear zygotes: a possible manifestation of androgenetic monospermic hydatidiform moles. F&S Reports. 2(2): 138–139.
Aguinagua M, Rezaei M, Monroy I, Mechtouf N, Perez J, Moreno E, Valespino Y, Galaz C, Razo G, Medina D, Pina R, Slim R. Genetics of recurrent hydatidiform moles in Mexico: evidence of a widespread founder effect for one variant in NLRP7, L750V, on a shared haplotype. J Assist Reprod Genet. 2021 Mar 22. doi: 10.1007/s10815-021-02132-1.
Rezaei M, Suresh B, Bareke E, Hadipour Z, Aguinagua M, Qian J, Bagga R, Fardaei M, Hemida R, Jagadeesh R, Majewski J, and Slim R*. Novel pathogenic variants in NLRP7, NLRP5 and PADI6 in patients with recurrent hydatidiform moles and reproductive failure. Clin Genet. 2021 Feb 14. doi: 10.1111/cge.13941.
Allias F, Mechtouf N, Gaillot-Durand L, Hoffner L, Hajri T, Devouassoux-Shisheboran M, Massardier J, Golfier F, Bolze PA, Surti U,Slim R. A novel NLRP7 protein-truncating mutation associated with discordant and divergent p57 immunostaining in diploid biparental and triploid digynic moles. Virchows Arch. 2020 Feb 13. doi: 10.1007/s00428-020-02769-w.
Khawajkie Y, Mechtouf N, Nguyen NMP, Rahimi R, Breguet M, Arseneau J, Ronnett BM, Hoffner L, Lazure F, Arnaud M, Peers F, Tan L, Abu Rafea B, Aguinagua M, Horowitz NS, Ao A, Tan SL, Brown R, Buckett W, Surti U, Hovanes K, Sahoo T, Sauthier P, Slim R. Comprehensive Analysis of 204 Sporadic Hydatidiform Moles: Revisiting Risk Factors and their Correlations with the Molar Genotypes. Mod Pathol, 2019 Dec 19. doi: 10.1038/s41379-019-0432-4
Yassemine Khawajkie, Nawel Mechtouf, Phuong Nguyen, Rima Slim*. (2019). Microsatellite DNA Genotyping and Flow Cytometry Ploidy Analyses of Formalin-Fixed Paraffin-Embedded Hydatidiform Molar Tissues. J Vis Exp. 2019 Oct 20;(152). doi: 10.3791/60366.
Nguyen NMP, Ge ZJ, Reddy R, Fahiminiya S, Sauthier P, Bagga R, Sahin FI, Mahadevan S, Osmond M, Breguet M, Rahimi K, Lapensee L, Hovanes K, Srinivasan R, Van den Veyver IB, Sahoo T, Ao A Majewski J, Taketo T, Slim R. (2018). Causative genes and mechanism of androgenetic hydatidiform moles. Am J Hum Genet 103 (5):740-75. doi: 10.1016/j.ajhg.2018.10.007.
Nguyen NMP, Bolze PA, and Slim R. (2019). Hydatidiform Moles. R. M. Laxer et al. (eds.), Textbook of Autoinflammation, In Textbook of Autoinflammation. Springer, doi: 10.1007/978-3-319-98605-0_27.
Desterke C, Slim R, Candelier JJ. (2018) A bioinformatics transcriptome meta-analysis reveals increased trophoblast differentiation in hydatidiform mole. Placenta. May;65:29-36. doi: 10.1016/j.placenta.2018.04.002. Epub 2018 Apr 7.
Qian JH, Nguyen NMP, Rezaei M, Huang B, Tao YL, Zhang XF, Cheng Q, Yang HJ, Ao A, Majewski J, Slim R*. Biallelic PADI6 variants linking infertility, miscarriages, and hydatidiform moles, Eur J Hum Genet. 2018 Jul;26(7):1007-1013. doi: 10.1038/s41431-018-0141-3. Epub 2018 Apr 25.
Nguyen NMP, Khawajkie Y, Mechtouf N, Rezaei M, Breguet M, Kurvinen E, Jagadeesh S, Solmaz AE, Aguinaga M, Hemida R, Harma MI, Rittore C, Rahimi K, Arseneau J, Hovanes K, Clisham R, Lenzi T, Scurry B, Addor M-C, Bagga R, Girardet-Nendaz G, Finci V, Poke G, Grimes L, Gregersen N, York K, Bolze P-A, Patel C, Mozdarani H, Puechberty J, Scotchie J, Fardaei M, Harma M, Gardner RJM, Sahoo T, Dudding-Byth T, Srinivasan R, Sauthier P, Slim R*. (2018) The genetics of recurrent hydatidiform moles: new insights and lessons from a comprehensive analysis of 113 patients. Mod Pathol. 31(7):1116-1130. doi: 10.1038/s41379-018-0031-9.
Khawajkie Y, Buckett W, Nguyen NMP, Mechtouf N, Ao A, Arseneau J, Slim R. (2017). Recurrent triploid digynic conceptions and mature ovarian teratomas: Are they different manifestations of the same genetic defect?. Genes Chromosomes Cancer. 2017 Dec;56(12):832-840. doi: 10.1002/gcc.22484. Epub 2017 Sep 1
Traboulsi W, Sergent F, Boufettal H, Brouillet S, Slim R, Hoffmann P, Benlahfid M, Zhou QY, Balboni G, Onnis V, Bolze PA, Salomon A, Sauthier P, Mallet F, Aboussaouira T, Feige JJ, Benharouga M, and Alfaidy N. (2017). Antagonism of EG-VEGF receptors is a novel targeted therapy for choriocarcinoma progression: in vitro, in vivo and in clinical studies. Clinical Cancer Research. 2017 Sep 12. doi: 10.1158/1078-0432.CCR-17-0811
Sills ES, Obregon-Tito AJ, Gao H, McWilliams TK, Gordon AT, Adams CA, Slim R. (2017). Pathogenic variant in NLRP7 (19q13.42) associated with recurrent gestational trophoblastic disease: Data from early embryo development observed during in vitro fertilization. Clin Exp Reprod Med. 44(1): 40-46.
Slim R, Khawajkie Y, Rahimi K, and Sauthier P. (2017). Genetics and Epigenetics of Hydatidiform Moles. Copyright © 2001 John Wiley & Sons, Ltd.eLS. DOI: 10.1002/9780470015902.a0026452 Published, Wiley Online Library, United States
Rezaei M, Nguyen NM, Foroughinia L, Dash P, Ahmadpour F, Verma IC, Slim R, Fardaei M. Two novel mutations in the KHDC3L gene in Asian patients with recurrent hydatidiform mole. Hum Genome Var. Sep 1;3:16027, 2016.
Reddy R, Nguyen NMP, Sarrabay G, Rezaei M, Rivas MCG , Kavasoglu A, Berkil H, Elshafey A, Nunez KP, Dreyfus H, Philippe M, Hadipour Z, Durmaz A, Eaton EE, Schubert B, Ulker V, Hadipour F, Ahmadpour F, Touitou I, Fardaei M, Slim R*. The genomic architecture of NLRP7 is Alu rich and predisposes to disease-associated large deletions. Eur J Hum Genet. 2016 Oct;24(10):1516. doi: 10.1038/ejhg.2016.96
Bolze PA and Slim R*. Circulating Tumor DNA: A Potential Novel Diagnostic Approach in Gestational Trophoblastic Neoplasia. EBiomedicine 4:11-12, 2016
Akoury E, Gupta N, Bagga R, Brown S, Déry C, Kabra M, Srinivasan R , Slim R*. Live Births in Women with Recurrent Hydatidiform Mole and Two NLRP7 Mutations. Reprod Biomed Online. Jul;31(1):120-4, 2015.
Akoury E, Zhang L, Ao A, Slim R*. NLRP7 and KHDC3L, the two maternal-effect proteins responsible for recurrent hydatidiform moles, co-localize to the oocyte cytoskeleton. Hum Reprod. Jan;30(1):159-69, 2015
Nguyen NM, Zhang L, Reddy R, Déry C, Arseneau J, Cheung A, Surti U, Hoffner L, Seoud M, Zaatari G, Bagga R, Srinivasan R, Coullin P, Ao A, Slim R*. Comprehensive genotype-phenotype correlations between NLRP7 mutations and the balance between embryonic tissue differentiation and trophoblastic proliferation. J Med Genet. 51(9):623-634, 2014
Singer H, Biswas A, Zimmer N, Messaed C, Oldenburg J, Slim R, El-Maarri O. NLRP7 inter-domain interactions: the NACHT-associated domain (NAD) is the physical mediator for oligomeric assembly. Mol Hum Reprod 20(10):990-1001, 2014
Nguyen NM, Slim R*. Genetics and Epigenetics of Recurrent Hydatidiform Moles: Basic Science and Genetic Counselling. Curr Obstet Gynecol Rep 3:55-64, 2014
Zhao W, Muhetaer A, Luo TF, Zhou W, Qi C; Chen, Zhang XF, Zhang ZF, Déry C, Slim R*, Qian J. Absence of C6orf221/KHDC3L mutations in Chinese patients with recurrent and sporadic hydatidiform moles. Cancer Genet. 206(9-10):327-329, 2013
Slim R*, Wallace EP. NLRP7 and the Genetics of Hydatidiform Moles: Recent Advances and New Challenges. Front Immunol 4:242, 2013
Candelier JJ, Frappart L, Diatta AL, Yadaden T, Cisse ML, Afoutou JM, Picard JY, Mennesson B, Slim R, Si-Tayeb K, Coullin P.Differential expression of E-cadherin, b-catenin, and Lewis x between invasive hydatidiform moles and post-molar choriocarcinomas. Virchows Arch 462(6):653-663, 2013
Brown L, Mount S, Reddy R, Slim R, Wong C, Jobanputra V, Clifford P, Merril L, Brown S. Recurrent pregnancy loss in a woman with NLRP7 mutation: Not all molar pregnancies can be classified as either “partial” or “complete” hydatidiform moles. Int. J. Gynecol Pathol 32(4):399-405, 2013
Reddy R, Akoury E, Phuong NM Nguyen, Abdul-Rahman OA, Déry C, Gupta N, Daley WP, Ao A, Landolsi H, Fisher R, Touitou I, Slim R*. Report of four new patients with protein truncating mutations in C6orf221/KHDC3L and co-localization with NLRP7, Eur J Hum Genet 21(9):957-964, 2013
Zakariyah A, Hou W, Slim R, Jerome-Majewska L. TMED2/p24β1 is expressed in all gestational stages of human placentas and in choriocarcinoma cell lines. Placenta .33(3):214-219, 2012
Slim R*. Do patients with single NLRP7 private variants have a genetic predisposition to hydatidiform moles and reproductive wastage? J Med Genet, eLetter, October 1, 2012
Slim R*, Coullin P, Diatta A-L, Chebaro W, Courtin D, Abdelhak S, Garcia A. NLRP7 and the Genetics of Postmolar Choriocarcinomas in Senegal. Mol Hum Reprod .18(1):52-56, 2012
Messaed C, Akoury E, Djuric U, Zeng J, Saleh M, Gilbert L, Seoud M, Qureshi S, Slim R*. NLRP7, a nucleotide oligomerization domain-like receptor protein, is required for normal cytokine secretion and co-localizes with Golgi and the microtubule-organizing center. J Biol Chem 286(50):43313-43323, 2011
Qian J, Cheng Q, Murdoch S, Xu C, Jin F, Chebaro W, Zhang X, Gao H, Zhu Y, Slim R*,Xie X. The Genetics of Recurrent Hydatidiform Moles in China: Correlations between NLRP7 Mutations, Molar Genotypes, and Reproductive Outcomes. Mol Hum Reprod 17(10):612-619, 2011
Slim R*, Ao A, Surti U, Zhang L, Hoffner L, Arseneau J, Cheung A, Chebaro W, Wischmeijer A. Recurrent Triploid and Dispermic Conceptions in Patients with NLRP7 Mutations. Placenta 32 (5) 409-412, 2011
Choufani S, Shapiro JS, Susiarjo M, Butcher DT, Grafodatskaya D, Ferreira JC, Pinto D, Scherer SW, Schaeffer L, Caniggia I, Beyene J, Slim R, Bartolomei MS, Weksberg R. A novel approach identifies new differentially methylated regions (DMRs) associated with imprinted genes. Genome Res 21 (3):465-476, 2011
Messaed C, Chebaro W, Brisset RDR, RittoreC, Cheung A, Arseneau J, Schneider A,Chen MF, Bernishke K, Surti U, Hoffner L, Sauthier P, Buckett W, Qian J, Lau NM,, Bagga R, Engert JC, Coullin P, Touitou I, and Slim R*. NLRP7 in the spectrum of reproductive wastage: rare non-synonymous variants confer genetic susceptibility to recurrent reproductive wastage. J Med Genet 48(8):540-548, 2011
Murdoch S and Slim R*. Revisiting the Pathology of Hydatidiform Moles: New Findings and the Mysteries That Remain. In Physiology of Mother-Fetus relationship, Eds: Lafond J and Vaillancourt C, Publisher: Research Sign Post, 2010
Slim R*, Bagga R, Chebaro W, Srinivasan R, Agarwal N. A strong founder effect for two NLRP7 mutations in the Indian population. Clin Genet 76(3):292-295, 2009
Deveault C, Qian J, Chebaro W, Ao A, Gilbert L, Mehio A, Khan R, Tan SL, Wischmeijer A, Coullin P, Xie X, Slim R*. NLRP7 mutations in women with diploid androgenetic and triploid moles: a proposed mechanism for mole formation. Hum Mol Genet 18(5):888-897, 2009
Milhavet F, Cuisset L, Hoffman H, El-Shanti H, Slim R.,Aksentijevich I, Lesage S, Waterham H, Wise C, Sarrauste de Menthière C, Touitou I. The Infevers auto-inflammatory mutation online registry: new genes and functions in the 2007 update. Hum Mutat. 29(6):803-820, 2008
Qian J, Deveault C, Bagga R, Xie X, Slim R*. Women Heterozygous for NALP7/NLRP7 Mutations Are at Risk for Reproductive Wastage: Report of Two New Mutations. Hum Mutat 28(7) 741, 2007
Slim R, Mehio A. The genetics of hydatidiform moles: new lights on an ancient disease. Clin Genet.2007;71(1):25–34.
Djuric U, El-Maarri O, Lamb B, Kuick R, Seoud M, Coullin P, Oldenburg J, Hanash S, Slim R*. Familial molar tissues due to mutations in the inflammatory gene, NALP7, have normal postzygotic DNA methylation. Hum Genet, 120(3):390-395, 2006
Murdoch S, Seoud M, Kircheisen R, Mazhar R, Slim R*. Detailed gene and allele content analysis of three homozygous KIR haplotypes. Tissue Antigens, 68 (1):72-77, 2006
Murdoch S, Djuric U, Mazhar B, Seoud M, Khan R, Kuick R, Bagga R, Kircheisen R, Ao A, Ratti B, Hanash S, Rouleau G, Slim R*. Mutations in NALP7, a maternal effect gene, result in recurrent hydatidiform moles and reproductive wastage in humans. Nature Genet 38(3): 300-302, 2006
El-Maarri O, Seoud M, Rivière JB, Oldenburg J, Walter J, Rouleau G, Slim R*. Patients with familial biparental hydatidiform moles have normal methylation at imprinted genes. Eur J Hum Genet 13:486-490, 2005
Slim R*., Fallahian M, Rivière JB, Zali MR: Evidence of a genetic heterogeneity of familial hydatidiform moles. Placenta 26 (1): 3-7, 2004
El-Maarri O, Seoud M, Coullin P, Herbiniaux U, Oldenburg J, Rouleau R, Slim R*.: Maternal alleles acquiring paternal methylation patterns in biparental complete hydatidiform moles. Hum Mol Genet 12(12):1405-1413, 2003
Van den Veyver IB, Norman B, Tran CQ, Bourjac J, Slim R.: The human homologue (PEG3) of the mouse paternally expressed gene 3 (Peg3) is maternally imprinted but not mutated in women with familial recurrent hydatidiform molar pregnancies. J Soc Gynecol Investig 8(5):305-313, 2001
Moglabey YB, Kircheisen R, Seoud M, El Mogharbel N, Van den Veyver I, Slim R*.: Genetic mapping of a maternal locus responsible for familial hydatidiform moles. Hum Mol Genet 8(4):667-671, 1999
Helwani MN, Seoud M, Zahed L, Zaatari G, Khalil A, Slim R*.: A familial case of recurrent hydatidiform molar pregnancies with biparental genomic contribution. Hum Genet 105(1-2):112-115, 1999