A molecular basis for variation in clinical severity of isolated growth hormone deficiency type II.

Context: Dominant-negative GH1 mutations cause familial isolated growth hormone deficiency type II (IGHD II), which is characterized by GH deficiency, occasional multiple anterior pituitary hormone deficiencies, and anterior pituitary hypoplasia. The basis of the variable expression and progression of IGHD II among relatives who share the same GH1 mutation is poorly understood.

Objective: We hypothesized that the cellular ratios of mutant/normal GH1 transcripts would correlate with the severity of the IGHD II phenotype.

Mutation analysis of the muscarinic cholinergic receptor genes in isolated growth hormone deficiency type IB.

Background: Isolated GH deficiency (IGHD) is familial in 5-30% of patients. The most frequent form (IGHD-IB) has autosomal recessive inheritance, and it is known that it can be caused by mutations in the GHRH receptor (GHRHR) gene or in the GH gene. However, most forms of IGHD-IB have an unknown genetic cause.