Novel mutations in LHCGR (luteinizing hormone/choriogonadotropin receptor): expanding the spectrum of mutations responsi
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GENETICS
Novel mutations in LHCGR (luteinizing hormone/choriogonadotropin receptor): expanding the spectrum of mutations responsible for human empty follicle syndrome Zhihua Zhang 1 & Ling Wu 2 & Feiyang Diao 3 & Biaobang Chen 4 & Jing Fu 5 & Xiaoyan Mao 2 & Zheng Yan 2 & Bin Li 2 & Jian Mu 1 & Zhou Zhou 1 & Wenjing Wang 1 & Lin Zhao 1 & Jie Dong 1 & Yang Zeng 1 & Jing Du 4 & Yanping Kuang 2 & Xiaoxi Sun 5 & Lin He 6 & Qing Sang 1,7 & Lei Wang 1,7,8 Received: 8 April 2020 / Accepted: 18 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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. Keywords LHCGR . Mutations . Empty follicle syndrome . Reproduction Zhihua Zhang and Feiyang Diao contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10815-020-01931-2) contains supplementary material, which is available to authorized users. * Qing Sang [email protected] * Lei Wang [email protected] 1
Institute of Pediatrics, Children’s Hospital of Fudan University and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology and Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200032, China
2
Reproductive Medicine Center, Shanghai Ninth Hospital, Shanghai Jiao Tong University, Shanghai 200011, China
3
The State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China
4
NHC Key Lab of Reproduction Regulation (Shanghai
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