Novel pathogenic variants in NLRP7, NLRP5, and PADI6 in patients with recurrent hydatidiform moles and reproductive failure. Issue 6 (23rd February 2021)

• Record Type: Journal Article
• Authors: Rezaei, Maryam; Suresh, Beena; Bereke, Eric; Hadipour, Zahra; Aguinaga, Monica; Qian, Jianhua; Bagga, Rashmi; Fardaei, Majid; Hemida, Reda; Jagadeesh, Sujatha; Majewski, Jacek; Slim, Rima
• Is Part Of: Clinical genetics. Volume 99:Issue 6(2021)
• Page Start: 823
• Page End: 828
• Publication Date: 2021-02-23
• Subjects: hydatidiform moles -- imprinting disorders -- infertility -- KHDC3L -- NLRP5 -- NLRP7 -- PADI6 -- SCMC; Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.13941
• Languages: English
• ISSNs: 0009-9163

Abstract

Abstract: Recurrent hydatidiform moles (RHMs) are human pregnancies with abnormal embryonic development and hyperproliferating trophoblast. Biallelic mutations in NLRP7 and KHDC3L, members of the subcortical maternal complex (SCMC), explain the etiology of RHMs in only 60% of patients. Here we report the identification of seven functional variants in a recessive state in three SCMC members, five in NLRP7, one in NLRP5, and one in PADI6 . In NLRP5, we report the first patient with RHMs and biallelic mutations. In PADI6, the patient had four molar pregnancies, two of which had fetuses with various abnormalities including placental mesenchymal dysplasia and intra‐uterine growth restriction, which are features of Beckwith‐Wiedemann syndrome and Silver Russell syndrome, respectively. Our findings corroborate recent studies and highlight the common oocyte origin of all these conditions and the continuous spectrum of abnormalities associated with deficiencies in the SCMC genes. Abstract : The subcortical maternal complex (SCMC) is a large protein complex that is essential for programing the oocyte genome and consequently normal embryonic development. Recessive mutations in the SCMC genes cause a wide spectrum of diseases ranging from infertility to live born children with imprinting disorders and including recurrent hydatidiform moles (RHMs) and miscarriages. Our data highlight the common oocyte origin of all these conditions and the primary consequence of its defects on deregulating trophoblast differentiation and proliferation.