ECEESPE2025 Poster Presentations Pituitary, Neuroendocrinology and Puberty (162 abstracts)
Phenotype and genotype of 23 patients with hypopituitarism and pathogenic GLI2 variants
AOUCHICHE Karine 1 , Charmensat Camille 2 , Cecile Thomas-Teinturier 3 , Patricia Bretones 4 , Aude Brac de la Perrier 4 , LAYET Valerie 5 , Bouhours-Nouet Natacha 6 , Marie-Christine VANTYGHEM 7 , HAINE ELSA 8 , Marie-Laure NUNES 9 , Camart Odile 10 , BARON SABINE 11 , Frederic Castinetti 12 , Anne Barlier 12 , Thierry Brue 13 , Rachel Reynaud 13 & Saveanu Alexandru 12
1Aix Marseille University, Assistance Publique-Hôpitaux de Marseille, Marseille, France; 2Assistance Publique-Hôpitaux de Marseille, Marseille, France; 3Assistance Publique-Hôpitaux de Paris AP-HP, Paris, France; 4Hospices Civils de Lyon, Lyon, France; 5Havre’s Hospital, Le Havre, France; 6University Hospital of Angers, Angers, France; 7University Hospital of Lille Department of Endocrinology, Lille, France; 8University Hospital of Nice-Lenval Hospital, Lille, France; 9University Hospital of Bordeaux Department Endocrinology, Bordeaux, France; 10Niort Hospital, Niort, France; 11University Hospital of Nantes, Nantes, France; 12Assistance Publique-Hôpitaux de Marseille, Aix Marseille university, MArseille, France; 13Assistance Publique-Hôpitaux de Marseille, Aix Marseille university, Marseille, France
JOINT1283
Aim: The objective of this study is to analyze the phenotype and genotype of patients diagnosed with congenital hypopituitarism and pathogenic GLI2 variants.
Methods: A 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.
Results: Pathogenic or likely pathogenic variants in GLI2 were identified in 17 out of 59 mutations reported from 717 index cases. GLI2 mutations were identified exclusively in patients with associated pituitary stalk interruption syndrome or extrapituitary signs (n = 440), representing the most frequent identified genetic cause in patients with syndromic pituitary deficiency. GLI2 variants were the most frequent 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 Kallman syndrome. Pituitary morphological abnormalities were present in 84% of the patients with pathogenic 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.
Conclusion: GLI2 has been identified as the most frequent genetic cause in congenital pituitary deficiency with pituitary stalk disruption syndrome or extrapituitary clinical feature. In addition to the commonly associated polydactyly and neurodevelopmental disorder, cardiac and renal abnormalities were frequently observed in these patients and should be investigated further. The variable expression of GLI2-associated phenotypes justifies further research in this area.
Volume 110
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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