ArticleThe Journal of clinical endocrinology and metabolism2013
Variations in PROKR2, but not PROK2, are associated with hypopituitarism and septo-optic dysplasia.
Article in The Journal of clinical endocrinology and metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 58 citations in OpenAlex.
- Management of Acquired Hypothalamic Dysfunction and the Hypothalamic Syndrome; It Is More Than Obesity.Endocrine reviews · 2025Review
- Appetite- and Weight-Regulating Neuroendocrine Circuitry in Hypothalamic Obesity.Endocrine reviews · 2024Review
- Article
- Phenotypic and genotypic landscape of PROKR2 in neuroendocrine disorders.Frontiers in endocrinology · 2023Review
- Comprehensive Identification of Pathogenic Gene Variants in Patients With Neuroendocrine Disorders.The Journal of clinical endocrinology and metabolism · 2021Article
- One4TwoGenes · 2021Observational
- Genetics of congenital hypogonadotropic hypogonadism: peculiarities and phenotype of an oligogenic disease.Human genetics · 2021Review
- Oligogenic Inheritance Underlying Incomplete Penetrance ofFrontiers in genetics · 2021Article
- Congenital Hypopituitarism During the Neonatal Period: Epidemiology, Pathogenesis, Therapeutic Options, and Outcome.Frontiers in pediatrics · 2020Review
- Genetic analysis of adult Slovenian patients with combined pituitary hormone deficiency.Endocrine · 2019Article
- Septo-optic dysplasia caused by a novel FLNA splice site mutation: a case report.BMC medical genetics · 2019Article
- Nervous System Malformations.Continuum (Minneapolis, Minn.) · 2018Review
- Sexually dimorphic distribution of Prokr2 neurons revealed by the Prokr2-Cre mouse model.Brain structure & function · 2017Article
- Paradoxical gain-of-function mutant of the G-protein-coupled receptor PROKR2 promotes early puberty.Journal of cellular and molecular medicine · 2017Article
- Genetics of Combined Pituitary Hormone Deficiency: Roadmap into the Genome Era.Endocrine reviews · 2016Review
- Spectrum of Clinical and Associated MR Imaging Findings in Children with Olfactory Anomalies.AJNR. American journal of neuroradiology · 2016Article
- Computational Analysis of Missense Variants of G Protein-Coupled Receptors Involved in the Neuroendocrine Regulation of Reproduction.Neuroendocrinology · 2016Article
- Novel application of luciferase assay for the in vitro functional assessment of KAL1 variants in three females with septo-optic dysplasia (SOD).Molecular and cellular endocrinology · 2015Article
- Recent advances in central congenital hypothyroidism.The Journal of endocrinology · 2015Review
- FGFR1 and PROKR2 rare variants found in patients with combined pituitary hormone deficiencies.Endocrine connections · 2015Article
Corrections and comments
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Authors and funding
16 authors at 8 institutions in 5 countries.
Funding
Abstract
contextLoss-of-function mutations in PROK2 and PROKR2 have been implicated in Kallmann syndrome (KS), characterized by hypogonadotropic hypogonadism and anosmia. Recent data suggest overlapping phenotypes/genotypes between KS and congenital hypopituitarism (CH), including septo-optic dysplasia (SOD).
objectiveWe screened a cohort of patients with complex forms of CH (n = 422) for mutations in PROK2 and PROKR2.
resultsWe detected 5 PROKR2 variants in 11 patients with SOD/CH: novel p.G371R and previously reported p.A51T, p.R85L, p.L173R, and p.R268C-the latter 3 being known functionally deleterious variants. Surprisingly, 1 patient with SOD was heterozygous for the p.L173R variant, whereas his phenotypically unaffected mother was homozygous for the variant. We sought to clarify the role of PROKR2 in hypothalamopituitary development through analysis of Prokr2(-/-) mice. Interestingly, these revealed predominantly normal hypothalamopituitary development and terminal cell differentiation, with the exception of reduced LH; this was inconsistent with patient phenotypes and more analogous to the healthy mother, although she did not have KS, unlike the Prokr2(-/-) mice.
conclusionsThe role of PROKR2 in the etiology of CH, SOD, and KS is uncertain, as demonstrated by no clear phenotype-genotype correlation; loss-of-function variants in heterozygosity or homozygosity can be associated with these disorders. However, we report a phenotypically normal parent, homozygous for p.L173R. Our data suggest that the variants identified herein are unlikely to be implicated in isolation in these disorders; other genetic or environmental modifiers may also impact on the etiology. Given the phenotypic variability, genetic counseling may presently be inappropriate.
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