Mutation of the kiss-1 gene responsible for combined hypopituitarism: a report of 3 cases

Hamdi Frikha; Mouna Elleuch; Hana Charfi; Nesrine Dhieb; Salah Dhoha Ben; Mariam Moalla; Wajdi Sefi; Kacem Akid Faten Haj; Fatma Mnif; Nadia Charfi; Mouna Mnif; Hassen Hadjkacem; Mohamed Abid; Majdoub Nabila Rekik

doi:10.1530/endoabs.99.EP690

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Endocrine Abstracts (2024) 99 EP690 | DOI: 10.1530/endoabs.99.EP690

ECE2024 Eposter Presentations Pituitary and Neuroendocrinology (214 abstracts)

Mutation of the kiss-1 gene responsible for combined hypopituitarism: a report of 3 cases

Hamdi Frikha ¹ , Mouna Elleuch ¹ , Hana Charfi ¹ , Nesrine Dhieb ¹ , Dhoha Ben Salah ¹ , Mariam Moalla ² , Wajdi Sefi ¹ , Faten Haj Kacem Akid ¹ , Fatma Mnif ¹ , Nadia Charfi ¹ , Mouna Mnif ¹ , Hassen Hadjkacem ³ , Mohamed Abid ¹ & Nabila Rekik Majdoub ¹

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¹Hedi Chaker University Hospital, Department of Endocrinology;²Center of Biotechnology of Sfax, Laboratory of Molecular and Cellular Screening Processes;³College of Sciences, University of Sharjah, Department of Applied Biology, United Arab Emirates

Introduction: The KISS1 gene codes for the G protein-coupled receptor 54 (KISS1R) and plays a crucial role in the regulation of reproduction and pubertal maturation. Mutations in the KISS1-R gene are extremely rare and usually implicated in isolated hypogonadotropic hypogonadism. Here, we report three cases of a familial mutation in the KISS1 gene responsible for combined hypopituitarism.

Observations: Three related patients (including two twins) from a first-degree consanguineous union presented with delayed puberty at the ages of 15 and 16, respectively. Clinical examination revealed growth retardation and the absence of pubertal development signs without anosmia. Exploration confirmed combined hypopituitarism in all three patients (complete growth hormone deficiency, gonadotropin deficiency, and corticotropin deficiency). Magnetic resonance imaging was normal for all patients. Genetic study showed a non-stop mutation c.1195T>C, p.X399R in the KISS1 gene.

Conclusion: This mutation was absent in 100 controls from the Tunisian population, as well as in all accessible international genomic databases, indicating a de novo character. These observations challenge the distinction between different forms of hypopituitarism, suggesting instead a phenotypic continuum and a multifaceted pathology.