Molecular and structural analysis of two novel STAR mutations in patients with lipoid congenital adrenal hyperplasia

Mutations in the gene encoding steroidogenic acute regulatory protein (StAR ) cause lipoid congenital adrenal hyperplasia. We report a novel homozygous splice site mutation (IVS1 + 2T --> G) in STAR in two sisters (46XY, 46XX) who presented with primary adrenal insufficiency at birth and a novel homo zygous R182H missense mutation in the putative lipid transfer domain of StA R in a phenotypic female (46XY) with adrenal failure and a parotid tumor. T hese cases highlight the importance of StAR-dependent steroidogenesis durin g fetal development and early infancy and of the critical functional role o f R182 in cholesterol transport. (C) 2001 Academic Press.