HESX1

Last update 08 May 2025

Basic Info

Synonyms

ANF, hAnf, HESX homeobox 1

+ [4]

Introduction

Required for the normal development of the forebrain, eyes and other anterior structures such as the olfactory placodes and pituitary gland. Possible transcriptional repressor. Binds to the palindromic PIII sequence, 5'-AGCTTGAGTCTAATTGAATTAACTGTAC-3'. HESX1 and PROP1 bind as heterodimers on this palindromic site, and, in vitro, HESX1 can antagonize PROP1 activation.

100 Clinical Results associated with HESX1

100 Translational Medicine associated with HESX1

0 Patents (Medical) associated with HESX1

266

Literatures (Medical) associated with HESX1

01 Feb 2025·European Journal of Endocrinology

Phenotype and genotype of 23 patients with hypopituitarism and pathogenic GLI2 variants

Article

Author: Haine, Elsa ; Vantyghem, Marie-Christine ; Nicolino, M ; Bouhours-Nouet, Natacha ; Jullien, Nicolas ; Morgane, Pertuit ; Daval Cote, M ; Linglard, A ; Aouchiche, Karine ; Abel, C ; Barat, P ; Brue, Thierry ; Brac de la Perriere, Aude ; Saveanu, Alexandru ; Baron, Sabine ; Coutant, R ; Bretones, Patricia ; Lambert, A-S ; Castinetti, Frederic ; Charmensat, Camille ; Layet, Valérie ; Barlier, Anne ; Camard, Odile ; Reynaud, Rachel ; Nunes-Sanchez, Marie-Laure ; Teinturier, Cécile

AbstractObjectiveTo analyze the phenotype and genotype of patients with congenital hypopituitarism (CH) and pathogenic (P) GLI2 variants.MethodsA large cohort of patients with hypopituitarism was screened for GLI2 variants using a next-generation sequencing panel. Genotype–phenotype correlations were then assessed using GENHYPOPIT phenotypic data.ResultsOf the 39 GLI2 variants identified in 717 index cases, 17 were classified as pathogenic and likely pathogenic. All these GLI2 variants were identified in 23 patients (17 index cases and 6 relatives) with associated pituitary stalk interruption syndrome or extrapituitary manifestations. GLI2 variants were the most frequently identified genetic cause in patients with syndromic hypopituitarism (68%): 88% (15/17) of mutations were truncating variants, and 45% were de novo. Most patients with a GLI2 variant (21/23, 91%) had hypopituitarism, including 21.7% (5/23) presenting isolated growth hormone deficiency. Two patients had Kallmann syndrome. Pituitary morphological abnormalities were present in 84% of the patients with P GLI2 variants (index cases and affected relatives). The remaining signs included neurocognitive disorders (38%), hexadactyly (27%), cardiac septal defects, and renal/vesical abnormalities. A possible digenic origin (GLI2/HESX1) is proposed in one family.ConclusionIn this large multicentric international cohort, GLI2 was the most frequently identified genetic cause of syndromic CH with constant association of pituitary stalk interruption syndrome or extrapituitary clinical features. In addition to polydactyly and neurocognitive disorders, cardiac and renal abnormalities were also frequently observed and should be investigated further. The variable expression of GLI2-associated phenotypes justifies further research in this area.

31 Dec 2024·Annals of Pediatric Endocrinology & Metabolism

Clinical and genetic features of childhood-onset congenital combined pituitary hormone deficiency: a retrospective, single-center cohort study

Article

Author: Lee, Young Ah ; Shin, Choong Ho ; Ko, Jung Min ; Lee, Yun Jeong ; Lee, Yoonha

Purpose: To investigate the clinical characteristics and genetic features of childhood-onset congenital combined pituitary hormone deficiency (cCPHD) in Korean patients.Methods: We retrospectively analyzed 444 patients diagnosed with childhood-onset CPHD at a tertiary center between 1994 and 2021. After excluding acquired case, 43 patients with cCPHD were enrolled. Anthropometric measurements, hormone evaluations, brain magnetic resonance imaging (MRI), extrapituitary phenotypes, and adult outcomes were analyzed. Genetic analyses were performed on 26 patients using a targeted gene panel or whole exome sequencing.Results: Mean age at diagnosis was 3.2 years, and 41.9% were diagnosed at less than 1 year old. Short stature was the most frequent (37.2%) initial presentation, and mean height z-score was -2.4. More than half (n=23, 53.5%) of patients had neonatal features suggestive of hypopituitarism; however, only 15 (65.2%) were diagnosed in infancy. Growth hormone deficiency (GHD) was prevalent in 42 (97.7%), and 33 (76.7%) had 3 or more hormone deficiencies. Extrapituitary phenotypes were identified in 31 (72.1%). Brain MRI abnormalities correlated with a higher number of hormone deficiencies (P for trend 0.049) and were present in 33 patients (80.5%). Adult GHD was diagnosed in all 17 investigated patients, and metabolic disturbances were noted in 10 (58.9%). Pathogenic variants in POU1F1, GLI2, HESX1, TBC1D32, and ROBO1 were found in 5 (19.2%).Conclusion: Considering the high proportion of neonatal presentations, identification of the early neonatal features of hypopituitarism to manage pituitary and extrapituitary phenotypes is critical. The genetic etiology of cCPHD warrants further exploration.

03 Oct 2024·Brain

Connecting dementia risk loci to the CSF proteome identifies pathophysiological leads for dementia

Article

Author: Meeter, Lieke H ; Irwin, David J ; Reus, Lianne M ; del Campo Milan, Marta ; Peeters, Carel F W ; Hok-A-Hin, Yanaika S ; Chen-Plotkin, Alice ; van Swieten, John C ; De Groot, Lisa A ; van der Flier, Wiesje M ; Jansen, Iris E ; van der Lee, Sven J ; Hu, William T ; Tijms, Betty M ; Holstege, Henne ; Lemstra, Afina W ; Pijnenburg, Yolande A L ; Hulsman, Marc ; Teunissen, Charlotte E ; Tesi, Niccoló ; Vermunt, Lisa ; Visser, Pieter Jelle

AbstractGenome-wide association studies have successfully identified many genetic risk loci for dementia, but exact biological mechanisms through which genetic risk factors contribute to dementia remains unclear. Integrating CSF proteomic data with dementia risk loci could reveal intermediate molecular pathways connecting genetic variance to the development of dementia.We tested to what extent effects of known dementia risk loci can be observed in CSF levels of 665 proteins [proximity extension-based (PEA) immunoassays] in a deeply-phenotyped mixed memory clinic cohort [n = 502, mean age (standard deviation, SD) = 64.1 (8.7) years, 181 female (35.4%)], including patients with Alzheimer’s disease (AD, n = 213), dementia with Lewy bodies (DLB, n = 50) and frontotemporal dementia (FTD, n = 93), and controls (n = 146). Validation was assessed in independent cohorts (n = 99 PEA platform, n = 198, mass reaction monitoring-targeted mass spectroscopy and multiplex assay). We performed additional analyses stratified according to diagnostic status (AD, DLB, FTD and controls separately), to explore whether associations between CSF proteins and genetic variants were specific to disease or not.We identified four AD risk loci as protein quantitative trait loci (pQTL): CR1-CR2 (rs3818361, P = 1.65 × 10−8), ZCWPW1-PILRB (rs1476679, P = 2.73 × 10−32), CTSH-CTSH (rs3784539, P = 2.88 × 10−24) and HESX1-RETN (rs186108507, P = 8.39 × 10−8), of which the first three pQTLs showed direct replication in the independent cohorts. We identified one AD-specific association between a rare genetic variant of TREM2 and CSF IL6 levels (rs75932628, P = 3.90 × 10−7). DLB risk locus GBA showed positive trans effects on seven inter-related CSF levels in DLB patients only. No pQTLs were identified for FTD loci, either for the total sample as for analyses performed within FTD only.Protein QTL variants were involved in the immune system, highlighting the importance of this system in the pathophysiology of dementia. We further identified pQTLs in stratified analyses for AD and DLB, hinting at disease-specific pQTLs in dementia. Dissecting the contribution of risk loci to neurobiological processes aids in understanding disease mechanisms underlying dementia.

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HESX1

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