ReviewThe Journal of clinical endocrinology and metabolism2017
Digenic Inheritance of PROKR2 and WDR11 Mutations in Pituitary Stalk Interruption Syndrome.
Review in The Journal of clinical endocrinology and metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Re-analysis of gene mutations found in pituitary stalk interruption syndrome and a new hypothesis on the etiology.Frontiers in endocrinology · 2024Pooled it
- Development of the neurohypophysis: A major neuroendocrine interface.Journal of neuroendocrinology · 2026Review
- Hypopituitarism: genetic, developmental, and acquired etiologies with a focus on the emerging concept of autoimmune hypophysitis.Endocrine journal · 2025Review
- A Novel Missense Variant inChildren (Basel, Switzerland) · 2025Article
- Digenic Inheritance of PROC and SERPINC1 Mutations Contributes to Multiple Sites Venous Thrombosis.Hamostaseologie · 2024Article
- Pulsatile gonadotropin-releasing hormone therapy induces spermatogenesis in pituitary stalk interruption syndrome: A case report and review of the literature.World journal of clinical cases · 2024Article
- Article
- Coordination of canonical and noncanonical Hedgehog signalling pathways mediated by WDR11 during primordial germ cell development.Scientific reports · 2023Article
- Exome sequencing in 16 patients with pituitary stalk interruption syndrome: A monocentric study.PloS one · 2023Article
- Phenotypic and genotypic landscape of PROKR2 in neuroendocrine disorders.Frontiers in endocrinology · 2023Review
- POU1F1/Pou1f1 c.143-83A > G Variant Disrupts the Branch Site in Pre-mRNA and Leads to Dwarfism.Endocrinology · 2022Article
- Article
- Novel Genomic Variants, Atypical Phenotypes and Evidence of a Digenic/Oligogenic Contribution to Disorders/Differences of Sex Development in a Large North African Cohort.Frontiers in genetics · 2022Article
- CDON gene contributes to pituitary stalk interruption syndrome associated with unilateral facial and abducens nerve palsy.Journal of applied genetics · 2021Article
- Advances in differential diagnosis and management of growth hormone deficiency in children.Nature reviews. Endocrinology · 2021Review
- The Differential Roles for Neurodevelopmental and Neuroendocrine Genes in Shaping GnRH Neuron Physiology and Deficiency.International journal of molecular sciences · 2021Review
- Diagnosis and Management of Central Congenital Hypothyroidism.Frontiers in endocrinology · 2021Review
- Evidence That the Etiology of Congenital Hypopituitarism Has a Major Genetic Component but Is Infrequently Monogenic.Frontiers in genetics · 2021Article
- Genetics of congenital hypogonadotropic hypogonadism: peculiarities and phenotype of an oligogenic disease.Human genetics · 2021Review
- Pituitary stalk interruption syndrome and liver changes: From clinical features to mechanisms.World journal of gastroenterology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Context: Pituitary stalk interruption syndrome (PSIS, ORPHA95496) is a congenital defect of the pituitary gland characterized by the triad of a very thin/interrupted pituitary stalk, an ectopic (or absent) posterior pituitary gland, and hypoplasia or aplasia of the anterior pituitary gland. Complex genetic patterns of inheritance of this disorder are increasingly recognized. Objective: The objective of this study was to identify a genetic cause of PSIS in an affected child. Methods: Whole exome sequencing (WES) was performed by using standard techniques, with prioritized genetic variants confirmed via Sanger sequencing. To investigate the effects of one candidate variant on mutant WDR11 function, Western blotting and coimmunofluorescence were used to assess binding capacity, and leptomycin B exposure along with immunofluorescence was used to assess nuclear localization. Results: We describe a child who presented in infancy with combined pituitary hormone deficiencies and whose brain imaging demonstrated a small anterior pituitary, ectopic posterior pituitary, and a thin, interrupted stalk. WES demonstrated heterozygous missense mutations in two genes required for pituitary development, a known loss-of-function mutation in PROKR2 (c.253C>T;p.R85C) inherited from an unaffected mother, and a WDR11 (c.1306A>G;p.I436V) mutation inherited from an unaffected father. Mutant WDR11 loses its capacity to bind to its functional partner, EMX1, and to localize to the nucleus. Conclusions: WES in a child with PSIS and his unaffected family implicates a digenic mechanism of inheritance. In cases of hypopituitarism in which there is incomplete segregation of a monogenic genotype with the phenotype, the possibility that a second genetic locus is involved should be considered.
Indexed as
Identifiers
What OpenQuestion holds
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.