ArticleHuman molecular genetics2012
An ancient founder mutation in PROKR2 impairs human reproduction.
Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00494169 (Molecular Basis of Inherited Reproductive Disorders), which is not on this map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Molecular Basis of Inherited Reproductive Disorders
Who cites it
18 citing papers in PubMed, 39 citations in OpenAlex.
- Expanding the phenotypic spectrum of PROK2/PROKR2: a recall-by-genotype study.Human genetics · 2025Article
- Genetic Polymorphisms of Prokineticins and Prokineticin Receptors Associated with Human Disease.Life (Basel, Switzerland) · 2024Review
- Illuminating the terminal nerve: Uncovering the link between GnRH-1 neuron and olfactory development.The Journal of comparative neurology · 2024Article
- High Population Frequency ofJournal of the Endocrine Society · 2024Article
- Therapeutic Potential of Targeting Prokineticin Receptors in Diseases.Pharmacological reviews · 2023Review
- Phenotypic and genotypic landscape of PROKR2 in neuroendocrine disorders.Frontiers in endocrinology · 2023Review
- Sex differences in the coexpression of prokineticin receptor 2 and gonadal steroids receptors in mice.Frontiers in neuroanatomy · 2022Article
- Correlation Analysis of Genotypes and Phenotypes in Chinese Male Pediatric Patients With Congenital Hypogonadotropic Hypogonadism.Frontiers in endocrinology · 2022Article
- One4TwoGenes · 2021Observational
- Modeling mutant/wild-type interactions to ascertain pathogenicity of PROKR2 missense variants in patients with isolated GnRH deficiency.Human molecular genetics · 2018Article
- Article
- Mutation Spectrum of STAR and a Founder Effect of the p.Q258* in Korean Patients with Congenital Lipoid Adrenal Hyperplasia.Molecular medicine (Cambridge, Mass.) · 2017Article
- Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort.Genome biology · 2016Article
- Withdrawn: Discovering Genes Essential to the Hypothalamic Regulation of Human Reproduction Using a Human Disease Model: Adjusting to Life in the "-Omics" Era.Endocrine reviews · 2016Review
- Discovering Genes Essential to the Hypothalamic Regulation of Human Reproduction Using a Human Disease Model: Adjusting to Life in the "-Omics" Era.Endocrine reviews · 2015Review
- Congenital Hypogonadotropic Hypogonadism and Kallmann Syndrome: Past, Present, and Future.Endocrinology and metabolism (Seoul, Korea) · 2015Review
- Expanding the Spectrum of Founder Mutations Causing Isolated Gonadotropin-Releasing Hormone Deficiency.The Journal of clinical endocrinology and metabolism · 2015Article
- TSHZ1-dependent gene regulation is essential for olfactory bulb development and olfaction.The Journal of clinical investigation · 2014Article
Corrections and comments
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Authors and funding
23 authors at 11 institutions in 7 countries.
Funding
Abstract
Congenital gonadotropin-releasing hormone (GnRH) deficiency manifests as absent or incomplete sexual maturation and infertility. Although the disease exhibits marked locus and allelic heterogeneity, with the causal mutations being both rare and private, one causal mutation in the prokineticin receptor, PROKR2 L173R, appears unusually prevalent among GnRH-deficient patients of diverse geographic and ethnic origins. To track the genetic ancestry of PROKR2 L173R, haplotype mapping was performed in 22 unrelated patients with GnRH deficiency carrying L173R and their 30 first-degree relatives. The mutation's age was estimated using a haplotype-decay model. Thirteen subjects were informative and in all of them the mutation was present on the same ~123 kb haplotype whose population frequency is ≤10%. Thus, PROKR2 L173R represents a founder mutation whose age is estimated at approximately 9000 years. Inheritance of PROKR2 L173R-associated GnRH deficiency was complex with highly variable penetrance among carriers, influenced by additional mutations in the other PROKR2 allele (recessive inheritance) or another gene (digenicity). The paradoxical identification of an ancient founder mutation that impairs reproduction has intriguing implications for the inheritance mechanisms of PROKR2 L173R-associated GnRH deficiency and for the relevant processes of evolutionary selection, including potential selective advantages of mutation carriers in genes affecting reproduction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.