THE MOLECULAR-GENETICS OF GROWTH-HORMONE DEFICIENCY

Although most cases of short stature associated with growth hormone (G H) deficiency are sporadic and idiopathic, some 5-30% have an affected first degree relative consistent with a genetic aetiology for the con dition. Several different types of mutational lesion in the pituitary- expressed growth hormone (GHI) gene have been described in affected in dividuals. This review focuses primarily on the GH1 mutational spectru m and its unusual features, discusses potential mechanisms of mutagene sis and pathogenesis, and examines the correlation between mutant geno type and clinical phenotype. The characterization of pathological lesi ons in several other pituitary-expressed genes that are epistatic to G H1 (POU1F1, PROP1 and GHRHR) has identified additional causes of GH de ficiency, the molecular genetics of which are also explored.