GPR54 Polymorphisms in Chinese Girls with Central Precocious Puberty

Luan, Xiaohui; Hong, Yu; Wei, Xing; Zhou, Yuxun; Wang, W.; Li, P.; Gan, Xiaohong Tracey; Wei, Dongzhi; Xiao, Junhua

doi:10.1159/000107511

Cited by 54 publications

(40 citation statements)

References 30 publications

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“…Activated mutations of KISS-1 and GPR54 genes had been shown to cause central precocious puberty resulting from early maturation of the hypothalamicpituitary-gonadal axis in human (14)(15)(16). The present study preliminarily showed an association between alleles B and D of GPR54 gene and sexual precocity and high litter size in Jining Grey goats.…”

supporting

confidence: 63%

Association Between Sexual Precocity and Alleles ofKISS-1andGPR54Genes in Goats

Feng

Zhao

Chu

et al. 2009

Animal Biotechnology

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KISS-1 and GPR54 were regarded as key regulators for the puberty onset and fundamental gatekeepers of sexual maturation in mammals. To explore the possible association between variations in KISS-1 and GPR54 with sexual precocity, mutation screening of exon 1 of KISS-1 and exon 1, exon 3, and partial exon 5 of GPR54 was performed in a sexual precocious breed (Jining Grey goats) and sexual late-maturing breeds (Inner Mongolia Cashmere, Angora, and Boer goats) by PCR-SSCP. The results showed that five novel mutations were identified in exon 1 and partial exon 5 of GPR54 including C96 T, T173C, G176A, G825A, and C981 T. The Jining Grey goats with genotype BB or AB had 1.07 (P < 0.05) or 0.40 (P < 0.05) kids more than those with AA. The Jining Grey goats with genotype DD or CD had 1.80 (P < 0.05) or 0.55 (P < 0.05) kids more than CC, respectively. The present study preliminarily showed an association between alleles B and D of GPR54 with high litter size and sexual precocity in Jining Grey goats.

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supporting

confidence: 63%

Association Between Sexual Precocity and Alleles ofKISS-1andGPR54Genes in Goats

Feng

Zhao

Chu

et al. 2009

Animal Biotechnology

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“…The A/G coding sequence SNP on the GPR54 (KISS1R) gene (dbSNP ID: rs10407968) was previously identified by others [22,33] in a population of male patients with idiopathic hypogonadotropic hypogonadism, but no association with this disorder was found. Moreover, this polymorphism has not been recorded in a large population of Chinese girls (24 girls randomly selected from 272 girls with ICPP vs. 288 unrelated normal girls) who were screened for GPR54 (KISS1R)'s SNPs through direct sequencing [34]. The discordance in these data between Chinese and Caucasian populations cannot be explained by a different frequency of rs10407968 polymorphism in the Chinese general population, since it is reported to be 13.3% for G allele and therefore it is not represented significantly lower than the 15.7% representing the frequency of this allele in the Caucasian population (χ 2 test, p = 0.3).…”

Section: Discussionmentioning

confidence: 99%

Absence of GPR54 and TACR3 Mutations in Sporadic Cases of Idiopathic Central Precocious Puberty

et al. 2014

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Background/Aims: Kisspeptin (KISS1)/GPR54 (KISSR) signaling complex and neurokinin B (NKB)/NKB receptor (TACR3) signaling have been proposed as an integral part of the network coordinating GnRH release. GPR54 (KISS1R) and TACR3 gene mutations have been described in cases of idiopathic hypogonadotrophic hypogonadism, while limited data exist on gain-of-function mutation in GPR54 (KISS1R) gene causing idiopathic central precocious puberty (ICPP). No data on TACR3 mutations in ICPP have been described so far. The aim of this study was to elucidate the possible impact of GPR54 (KISS1R) and TACR3 mutations in ICPP. Methods: PCR-amplified genomic DNA of 38 girls with ICPP was analyzed for GPR54 and TACR3 gene mutations. Results: No GPR54 or TACR3 mutations were found. The A/G coding sequence single nucleotide polymorphism (SNP) on the GPR54 gene (dbSNP ID: rs10407968) was found in 2 patients with ICPP. Conclusion: Our data indicate that GPR54 and TACR3 gene mutations are not a frequent cause of ICPP. The identified A/G synonymous SNP (dbSNP ID: rs10407968) located in exon 1 of the gene is not likely to have a pathogenic role in exon splicing and therefore in the premature initiation of puberty.

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“…A KISS1R mutation (Pro196His) located in the second extracellular loop of the receptor was identified (49), as was a kisspeptin variant (Pro110Thr). No functional studies have been performed for either mutation, so the mechanism by which these mutations might be associated with precocious puberty remains to be elucidated (49,50).…”

Section: Figmentioning

confidence: 99%

KISS1R Intracellular Trafficking and Degradation: Effect of the Arg386Pro Disease-Associated Mutation

Bianco¹,

Vandepas

Correa-Medina

et al. 2011

Endocrinology

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The goal of this study was to investigate how the Arg386Pro mutation prolongs KiSS-1 receptor (KISS1R) responsiveness to kisspeptin, contributing to human central precocious puberty. Confocal imaging showed colocalization of wild-type (WT) KISS1R with a membrane marker, which persisted for up to 5 h of stimulation. Conversely, no colocalization with a lysosome marker was detected. Also, overnight treatment with a lysosome inhibitor did not affect WT KISS1R protein, whereas overnight treatment with a proteasome inhibitor increased protein levels by 24-fold. WT and Arg386Pro KISS1R showed time-dependent internalization upon stimulation. However, both receptors were recycled back to the membrane. The Arg386Pro mutation did not affect the relative distribution of KISS1R in membrane and internalized fractions when compared to WT KISS1R for up to 120 min of stimulation, demonstrating that this mutation does not affect KISS1R trafficking rate. Nonetheless, total Arg386Pro KISS1R was substantially increased compared with WT after 120 min of kisspeptin stimulation. This net increase was eliminated by blockade of detection of recycled receptors, demonstrating that recycled receptors account for the increased responsiveness of this mutant to kisspeptin. We therefore conclude the following: 1) WT KISS1R is degraded by proteasomes rather than lysosomes; 2) WT and Arg386Pro KISS1R are internalized upon stimulation, but most of the internalized receptors are recycled back to the membrane rather than degraded; 3) the Arg386Pro mutation does not affect the rate of KISS1R traffickinginstead, it prolongs responsiveness to kisspeptin by decreasing KISS1R degradation, resulting in the net increaseonmutantreceptorrecycledbacktotheplasmamembrane

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GPR54 Polymorphisms in Chinese Girls with Central Precocious Puberty

Cited by 54 publications

References 30 publications

Association Between Sexual Precocity and Alleles ofKISS-1andGPR54Genes in Goats

Association Between Sexual Precocity and Alleles ofKISS-1andGPR54Genes in Goats

Absence of GPR54 and TACR3 Mutations in Sporadic Cases of Idiopathic Central Precocious Puberty

KISS1R Intracellular Trafficking and Degradation: Effect of the Arg386Pro Disease-Associated Mutation

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