PROKR2 Variants in Multiple Hypopituitarism with Pituitary Stalk Interruption

Reynaud, Rachel; Jayakody, Sujatha A.; Monnier, Carine; Saveanu, Alexandru; Bouligand, Jérôme; Guedj, A.M.; Simonin, G.; Lecomte, P.; Barlier, Anne; Rondard, Philippe; Martinez-Barbera, Juan Pedro; Guiochon‐Mantel, Anne; Brue, Thierry

doi:10.1210/jc.2011-3056

Cited by 74 publications

(59 citation statements)

References 22 publications

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“…Interestingly, renal agenesis has not been reported in patients with PROKR2 mutations (30). This study confirms the high phenotypic heterogeneity of disorders associated with PROKR2 and PROK2 loss of function mutations (31,32).…”

Section: Discussionsupporting

confidence: 79%

PROKR2 and PROK2 mutations cause isolated congenital anosmia without gonadotropic deficiency

Moya‐Plana

Villanueva

Laccourreye

et al. 2013

European Journal of Endocrinology

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Objective: Isolated congenital anosmia (ICA) is a rare phenotype defined as absent recall of any olfactory sensations since birth and the absence of any disease known to cause anosmia. Although most cases of ICA are sporadic, reports of familial cases suggest a genetic cause. ICA due to olfactory bulb agenesis and associated to hypogonadotropic hypogonadism defines Kallmann syndrome (KS), in which several gene defects have been described. In KS families, the phenotype may be restricted to ICA. We therefore hypothesized that mutations in KS genes cause ICA in patients, even in the absence of family history of reproduction disorders. Design and methods: In 25 patients with ICA and olfactory bulb agenesis, a detailed phenotype analysis was conducted and the coding sequences of KAL1, FGFR1, FGF8, PROKR2, and PROK2 were sequenced. Results: Three PROKR2 mutations previously described in KS and one new PROK2 mutation were found. Investigation of the families showed incomplete penetrance of these mutations. Conclusions: This study is the first to report genetic causes of ICA and indicates that KS genes must be screened in patients with ICA. It also confirms the considerable complexity of GNRH neuron development in humans.

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Section: Discussionsupporting

confidence: 79%

PROKR2 and PROK2 mutations cause isolated congenital anosmia without gonadotropic deficiency

Moya‐Plana

Villanueva

Laccourreye

et al. 2013

European Journal of Endocrinology

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“…Given the roles of PROK2 and PROKR2 in angiogenesis, it was plausible to consider that mutations of such genes could be observed in patients with PSIS. Our group reported for the first time three heterozygous PROKR2 variants (L173R, R85H, A51T) in patients with GH, TSH and ACTH deficiencies (in some of them); MRI showed PSIS in all patients (20). Later on, McCabe et al reported five other PROKR2 variants (p.A51T, p.R85L, p.L173R, and p.R268C, p.G371R) in 11 patients with SOD and congenital hypopituitarism (from isolated GH deficiency to panhypopituitarism).…”

Section: Novel Aetiologies Involving Actors Known To Be Associated Wimentioning

confidence: 88%

MECHANISMS IN ENDOCRINOLOGY: An update in the genetic aetiologies of combined pituitary hormone deficiency

Castinetti¹,

Reynaud²,

Saveanu³

et al. 2016

European Journal of Endocrinology

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Over the last 5 years, new actors involved in the pathogenesis of combined pituitary hormone deficiency in humans have been reported: they included a member of the immunoglobulin superfamily glycoprotein and ciliary G protein-coupled receptors, as well as new transcription factors and signalling molecules. New modes of inheritance for alterations of genes encoding transcription factors have also been described. Finally, actors known to be involved in a very specific phenotype (hypogonadotroph hypogonadism for instance) have been identified in a wider range of phenotypes. These data thus suggest that new mechanisms could explain the low rate of aetiological identification in this heterogeneous group of diseases. Taking into account the fact that several reviews have been published in recent years on classical aetiologies of CPHD such as mutations of POU1F1 or PROP1, we focused the present overview on the data published in the last 5 years, to provide the reader with an updated review on this rapidly evolving field of knowledge.

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“…Pathogenic germline PROKR2 mutations associated with central hypogonadism have been identified to cause modulation of distinct intracellular pathways (biased signaling modulation) (Libri et al 2014, Sbai et al 2014, whereby the PROKR2 wild type activates different G-protein subtypes (Chen et al 2005). PROKR2 variants have been further described in patients with idiopathic combined pituitary hormone deficits (CPHD) including gonadotropin deficiency (Raivio et al 2012, Reynaud et al 2012. The PROKR2 also forms constitutive homomers in vivo ( Marsango et al 2011), and specific protomer-protomer interfaces for the oligomer have been suggested ( Sposini et al 2015).…”

Section: R68 Reviewmentioning

confidence: 99%

Oligomerization of GPCRs involved in endocrine regulation

Kleinau¹,

Müller²,

Biebermann³

2016

J Mol Endocrinol

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PROKR2 Variants in Multiple Hypopituitarism with Pituitary Stalk Interruption

Abstract: We report PROKR2 variants in congenital hypopituitarism with pituitary stalk interruption, suggesting a potential role of the prokineticin pathway in pituitary development.

Cited by 74 publications

References 22 publications

PROKR2 and PROK2 mutations cause isolated congenital anosmia without gonadotropic deficiency

PROKR2 and PROK2 mutations cause isolated congenital anosmia without gonadotropic deficiency

MECHANISMS IN ENDOCRINOLOGY: An update in the genetic aetiologies of combined pituitary hormone deficiency

Oligomerization of GPCRs involved in endocrine regulation

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