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 homozygous R182H missense mutation in the putative lipid transfer domain of StAR in a phenotypic female (46XY) with adrenal failure and a parotid tumor. These cases highlight the importance of StAR-dependent steroidogenesis during fetal development and early infancy and of the critical functional role of R182 in cholesterol transport.
Achermann
J C
JC
Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Medical School, 250 East Superior Street, Chicago, IL 60611, USA.
Meeks
J J
JJ
Jeffs
B
B
Das
U
U
Clayton
P E
PE
Brook
C G
CG
Jameson
J L
JL
D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D002675:Child, Preschool; D003241:Consanguinity; D005091:Exons / Q000235:genetics; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D008297:Male; D008958:Models, Molecular; D009679:Nuclear Family; D010375:Pedigree; D010750:Phosphoproteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D011487:Protein Conformation; D012671:Seminiferous Tubules / Q000737:chemistry / Q000473:pathology; D000098682:Steroidogenic Acute Regulatory Protein
D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein