Genetic screening of a Dutch population with isolated GH deficiency (IGHD)

Summary Objective Five per cent to 30% of cases of idiopathic isolated GH deficiency (IGHD) have first‐degree relatives with short stature, which is suggestive of a genetic aetiology. The HYPOPIT study aimed to obtain an overall picture of gene encoding pituitary GH (GH1) and gene encoding GH releasing hormone‐receptor (GHRHR) defects in a Dutch IGHD cohort and to relate them with clinical parameters. Design, patients and measurements Genetic analysis was performed of exons and exon–intron boundaries of GH1 and GHRHR in 89 Caucasian IGHD patients from 81 families, using denaturing high‐performance liquid chromatography (dHPLC), DNA sequencing and multiplex ligation‐dependent probe amplification. In addition, we performed functional studies on novel identified GH1 exonic variants. Results Five different heterozygous GH1 mutations were present in 5 out of 81 participating families (6·1%), whereas no mutations in GHRHR were found. Patients with IGF‐I SDS