• PMID: 22002533
• Gene Name: LHCGR
• Condition: Infertility
• Association: These results indicated that LHR-Del7 does not have a dominant negative effect on LHR-WT cell surface expression, and although the pathological splicing variant LHR-Del7 was able to localize to cell membranes it failed to bind hCG and had no effect on wil
• Mutation: IVS6-3C>A (-3 acceptor splice site of intron 6 of LHR)
• Population size: 1
• Population details: 1 patient
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Leydig cell hypoplasia

Functional study of an aberrant splicing variant of the human luteinizing hormone (LH) receptor

Han B, Wang ZQ, Xue LQ, Ma JH, Liu W, Liu BL, Wu JJ, Pan CM, Chen X, Zhao SX, Lu YL, Wu WL, Qiao J, Song HD.

The luteinizing hormone receptor (LHR) is a member of a subfamily of G protein-coupled receptors that is characterized by its alternative splicing. In a previous study, we identified a splice site mutation of intron 6 (IVS6-3C>A) in a patient suffering from Leydig cell hypoplasia, which leads to aberrant splicing of LHR mRNA. In vitro expression analysis confirmed that this mutation results in the skipping of exon 7 in the mature mRNA of the LHR gene. In this study, we determined the impact of IVS6-3C>A on the RNA secondary structure and function of LHR-Del7. The three-dimensional structure of the leucine-rich repeats in LHR was predicted by molecular modeling. Radioactive ligand-binding assays verified that LHR-Del7 has no binding affinity for hCG. Furthermore, we detected negligible cAMP production in cells transfected with LHR-Del7. Cells co-expressing LHR-WT and LHR-Del7 were able to generate cAMP in response to hCG, but there was no significant difference between cells transfected with LHR-WT/vector and LHR-WT/LHR-Del7, although the variant was able to localize to cell surface, similar to wild-type receptor. These results indicated that LHR-Del7 does not have a dominant negative effect on LHR-WT cell surface expression, and although the pathological splicing variant LHR-Del7 was able to localize to cell membranes it failed to bind hCG and had no effect on wild-type LHR. FAU - Han, Bing AU - Han B AD - State Key Laboratory of Medical Genomics, Molecular Medical Center, Shanghai Institute of Endocrinology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China. FAU - Wang, Zhi-quan AU - Wang ZQ FAU - Xue, Li-qiong AU - Xue LQ FAU - Ma, Jun-hua AU - Ma JH FAU - Liu, Wei AU - Liu W FAU - Liu, Bing-li AU - Liu BL FAU - Wu, Jia-jun AU - Wu JJ FAU - Pan, Chun-ming AU - Pan CM FAU - Chen, Xia AU - Chen X FAU - Zhao, Shuang-xia AU - Zhao SX FAU - Lu, Ying-li AU - Lu YL FAU - Wu, Wan-ling AU - Wu WL FAU - Qiao, Jie AU - Qiao J