Novel mutations in LHCGR (luteinizing hormone/choriogonadotropin receptor): expanding the spectrum of mutations responsible for human empty follicle syndrome

PURPOSE: To screen novel mutations in LHCGR responsible for empty follicle syndrome and explore the pathological mechanism of mutations. METHODS: Four affected individuals diagnosed with infertility-associated anovulation or oligo-ovulation from three independent families were recruited. Sanger sequencing was used to identify the LHCGR mutations in affected individuals. Western blot was performed to evaluate the effects of mutations on LHCGR protein levels. Immunofluorescence was done to explore the effects of mutations on LHCGR subcellular localization. The ATP levels were measured to infer the functional effects of the mutations on LHCGR. RESULTS: In the present study, three novel biallelic mutations in LHCGR were identified in four affected individuals from three independent families with empty follicle syndrome or oligo-ovulation. All biallelic mutations were inherited from the proband of their parents. The western blot showed that the identified mutations decreased LHCGR protein level and altered the glycosylation pattern. The immunofluorescence showed an ectopic subcellular localization of LHCGR in cultured HeLa cells. Besides, the mutations in LHCGR also reduced the cellular ATP consumption. CONCLUSION: These findings confirm previous studies and expand the mutational spectrum of LHCGR, which will provide genetic diagnostic marker for patients with empty follicle syndrome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10815-020-01931-2) contains supplementary material, which is available to authorized users.