Clinical Importance of Identification of PROP1 Gene Mutations in Children with Inherited Growth Hormone Deficiency
Abstract
Objective: PROP1 gene is the transcription factor regulating the differentiation of anterior pituitary cells during embryologic development. Mutations found in this gene are the most frequent cause of inherited pituitary hormone deficiency in the Middle and Eastern Europe.
The aim of this study was to identify the individuals with PROP1 gene mutations in the group of children with idiopathic combined pituitary hormone deficiency and with isolated growth hormone deficiency. Secondly, we evaluated clinical importance of PROP1 gene molecular genetic analysis.
Patients and methods: We collected DNA samples and phenotypic data of 94 patients with isolated growth hormone deficiency and of 55 patients with combined pituitary hormone deficiency treated in six Czech and one foreign centre. In patients with isolated deficiency we performed a screening method to detect two most frequent PROP1 gene mutations; DNA samples of patients with combined deficiency were subjected to direct PROP1 gene sequencing.
Results: In the group of 55 patients with combined pituitary hormone deficiency four were homozygous for 296delGA mutation; no other mutation was found in the rest of the group. In the group of 94 patients with isolated growth hormone deficiency one was heterozygous for 296delGA mutation.
Conclusions: This study has not confirmed the clinical importance of routine identification of PROP1 gene mutations in the phenotypic heterogeneous group of patients with idiopathic isolated or combined growth hormone deficiency. It may play a role in subjects with precisely defined phenotype.