Endocrine disorders associated with mutations in guanine nucleotide binding proteins

Abstract

The basis for a number of relatively rare endocrine diseases, which present clinically with features of AHO, have been shown conclusively to result from mutations in the G3 alpha gene which interfere with the expression of functional protein. Individual kindreds display a range of specific mutations in this gene. A further series of disorders result from somatic mutations of the G3 alpha gene which result in constitutive activation (in one case probably with a concomitant decrease in stability of the expressed protein). When such a mutation occurs in early embryogenesis it can result in a pattern of mosaicism of expression of clinical features in the patient. Despite these cases, equivalent alterations in other G-protein alpha subunit genes seem to be of limited importance in human disease. This is despite biochemical data from a range of experimental cell models which indicate that such mutations can have potent effects on cell growth and division.