The retrospective data analysis of NLRP7 and KHDC3L mutations in Turkish patients with recurrent hydatidiform mole.

Objective: Recurrent hydatidiform mole (RHM) is a rare disorder which is characterized by the presence of at least two molar pregnancies. The mutations in the NLRP7 and KHDC3L genes are responsible for the majority of recurrent molar pregnancies. This study aimed to demonstrate the diversity and frequency of NLRP7 and KHDC3L gene mutations in our Turkish cohort with recurrent molar pregnancies, and to establish genotype-phenotype correlation.

Materials and methods: It was aimed to represent the detected NLRP7 and KHDC3L gene variants and reproductive history of 32 recurrent mole hydatidiform patients. We analysed the retrospective clinical and sequence data of 32 patients, who were referred to the laboratory for NLRP7 and KHDC3L sequencing.

Results: Among the detected 32 patients with recurrent molar pregnancy, 18 of 32 patients had no mutation in these two genes; we found 7 cases of homozygous NLRP7 variant, 1 case of heterozygous NLRP77 variant, 3 cases of homozygous KHDC3L gene variant, and 1 case of heterozygous KHDC3L gene variant. Among the detected NLRP7 variants, 3 of 11 variants were classified as pathogenic, 7 of 11 variants were classified as likely pathogenic, and 1 of 11 variants was classified as variant of unknown significance (VUS). Among the detected KHDC3L variants, 1 of 4 was classified as pathogenic, 2 of 4 were classified as likely pathogenic, and 1 of 4 was classified as VUS. Seven unpublished NLRP7 gene variants and two unpublished KHDC3L gene variants were first reported in this study.

Conclusion: Here we report new RHM patients with NLRP7 and KHDC3L mutations. The current study highlights the importance of defining new cases and novel mutations in the pathogenesis and clinical management of RHM. Understanding genotype-phenotype correlations in RHM patients will also contribute to the selection of treatment methods and patient management.