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Novel pathogenic variants in NLRP7 , NLRP5 , and PADI6 in patients with recurrent hydatidiform moles and reproductive failure
Author(s) -
Rezaei Maryam,
Suresh Beena,
Bereke Eric,
Hadipour Zahra,
Aguinaga Monica,
Qian Jianhua,
Bagga Rashmi,
Fardaei Majid,
Hemida Reda,
Jagadeesh Sujatha,
Majewski Jacek,
Slim Rima
Publication year - 2021
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13941
Subject(s) - biology , genetics , mutation , gene , etiology , medicine
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.