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Article Dans Une Revue Journal of Clinical Endocrinology and Metabolism Année : 2012

PROKR2 Variants in Multiple Hypopituitarism with Pituitary Stalk Interruption.

Résumé

Context:Pituitary stalk interruption represents a frequent feature of congenital hypopituitarism, but only rare cases have been assigned to a known genetic cause.Objective:Using a candidate gene approach, we tested several genes as potential causes of hypopituitarism with pituitary stalk interruption. We hypothesized that ectopic posterior pituitary may be a consequence of defective neuronal axon projections along the pituitary stalk or defective angiogenesis of hypophyseal portal circulation. Considering the role of the prokineticin 2 pathway in angiogenesis and neuronal migration, we screened PROK2 and PROKR2 genes.Design:PROK2 and PROKR2 and all genes previously known to be involved in hypopituitarism with pituitary stalk interruption (LHX4, HESX1, OTX2, and SOX3) were screened in 72 index cases with pituitary stalk interruption syndrome from the GENHYPOPIT database. In vitro studies were performed to assess the functional consequences of allelic variants.Results:We identified two heterozygous PROKR2 mutations (p.Leu173Arg and p.Arg85His) previously reported in isolated hypogonadotroph hypogonadism and a novel PROKR2 variant (p.Ala51Thr) that, in contrast with both other mutations, did not impair receptor signaling activity. Three allelic variants of HESX1 were identified: the heterozygous p.Phe156Ser and the homozygous p.Arg109X mutations were functionally deleterious, whereas p.Ser67Thr was found as a rare allelic variant in association with p.Arg85His PROKR2 mutation in the same patient.Conclusions:We report PROKR2 variants in congenital hypopituitarism with pituitary stalk interruption, suggesting a potential role of the prokineticin pathway in pituitary development.

Dates et versions

hal-00701550 , version 1 (25-05-2012)

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Rachel Reynaud, Sujatha A Jayakody, Carine Monnier, Alexandru Saveanu, Jérome Bouligand, et al.. PROKR2 Variants in Multiple Hypopituitarism with Pituitary Stalk Interruption.. Journal of Clinical Endocrinology and Metabolism, 2012, epub ahead of print. ⟨10.1210/jc.2011-3056⟩. ⟨hal-00701550⟩
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