Clinical, Neuroradiological and Molecular Genetic Characteristics of 13 Patients Followed up for Growth Hormone Deficiency

Öz

Objective: Growth hormone-releasing hormone (GHRH) and somatostatin are hypothalamic peptides that regulate pulsatile growth hormone (GH) secretion. GHRH binding to its receptor activates signaling, promoting cell proliferation, GH synthesis, and secretion. Mutations in the growth hormone-releasing hormone receptor (GHRHR) and growth hormone 1 (GH1) genes, which are involved in this pathway, occur as a rare cause of isolated growth hormone deficiency (IGHD). This study aimed to evaluate the clinical features, neuroradiological findings, and molecular genetic test results of 13 patients diagnosed with IGHD, as well as their responses to growth hormone treatment. Methods: The study included 13 patients from six different consanguineous families who were being followed for isolated growth hormone deficiency. Using next-generation sequencing, biallelic disease-causing variants in the GHRHR and GH1 genes were identified in these patients. Clinical findings, family history, parental consanguinity, and neuroradiological images of the patients were retrospectively obtained from hospital records. Results: Biallelic variants were identified in the GHRHR gene in nine patients and in the GH1 gene in four patients. The potential impact of these variants on protein structure was assessed using in silico prediction tools, including SIFT, MutationTaster, REVEL, and PolyPhen-2. Conclusion: Screening for variants in the GH1 and GHRHR genes is recommended for patients with severe growth retardation, short stature. It is important to consider the possibility of multiple affected individuals presenting with similar phenotypes, particularly in regions with a high prevalence of consanguineous marriages. Therefore, comprehensive family screening should be conducted when appropriate.

Anahtar Kelimeler

• GH1
• GHRHR
• Consanguineous marriage
• short stature

Kaynakça

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