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

Abstract

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.