The genetics of recurrent hydatidiform moles: new insights and lessons from a comprehensive analysis of 113 patients

Article Article scientifique Article The genetics of recurrent hydatidiform moles: new insights and lessons from a comprehensive analysis of 113 patients eng 2018 author Nguyen Ngoc Minh Phuong author Khawajkie Yassemine author Mechtouf Nawel author Rezaei Maryam author Breguet Magali author Kurvinen Elvira author Jagadeesh Sujatha author Solmaz Asli Ece author Aguinaga Monica author Hemida Reda author Harma Mehmet Ibrahim author Rittore Cécile author Rahimi Kurosh author Arseneau Jocelyne author Hovanes Karine author Clisham Ronald author Lenzi Tiffanee author Scurry Bonnie author Addor Marie-Claude author Bagga Rashmi author Girardet Nendaz Geneviève Juliane 33707 author Finci Vildana 26778 author Poke Gemma author Grimes Leslie author Gregersen Nerine author York Kayla author Bolze Pierre-Adrien author Patel Chirag author Mozdarani Hossein author Puechberty Jacques author Scotchie Jessica author Fardaei Majid author Harma Muge author Gardner R J McKinlay author Sahoo Trilochan author Dudding-Byth Tracy author Srinivasan Radhika author Sauthier Philippe author Slim Rima 1116-1130 10.1038/s41379-018-0031-9 29463882 0893-3952 Hydatidiform mole is an aberrant human pregnancy characterized by early embryonic arrest and excessive trophoblastic proliferation. Recurrent hydatidiform moles are defined by the occurrence of at least two hydatidiform moles in the same patient. Fifty to eighty percent of patients with recurrent hydatidiform moles have biallelic pathogenic variants in NLRP7 or KHDC3L. However, in the remaining patients, the genotypic types of the moles are unknown. We characterized 80 new hydatidiform mole tissues, 57 of which were from patients with no mutations in the known genes, and we reviewed the genotypes of a total of 123 molar tissues. We also reviewed mutation analysis in 113 patients with recurrent hydatidiform moles. While all hydatidiform moles from patients with biallelic NLRP7 or KHDC3L mutations are diploid biparental, we demonstrate that those from patients without mutations are highly heterogeneous and only a small minority of them are diploid biparental (8%). The other mechanisms that were found to recur in patients without mutations are diploid androgenetic monospermic (24%) and triploid dispermic (32%); the remaining hydatidiform moles were misdiagnosed as moles due to errors in the analyses and/or their unusual mechanisms. We compared three parameters of genetic susceptibility in patients with and without mutations and show that patients without mutations are mostly from non-familial cases, have fewer reproductive losses, and more live births. Our data demonstrate that patients with recurrent hydatidiform moles and no mutations in the known genes are, in general, different from those with mutations; they have a milder genetic susceptibility and/or a multifactorial etiology underlying their recurrent hydatidiform moles. Categorizing these patients according to the genotypic types of their recurrent hydatidiform moles may facilitate the identification of novel genes for this entity. Dewey 618 58 Département de pédiatrie, gynécologie et obstétrique 223 false Modern Pathology 31 7 fc6c838d-a522-4b19-8b9e-6db00c565837 Article (Published version) Restricted Article.pdf 2523543 application/pdf restrictedAccess Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique

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The genetics of recurrent hydatidiform moles: new insights and lessons from a comprehensive analysis of 113 patients	Modern Pathology			2018	423	0

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