title: Mutations in the steroidogenic acute regulatory protein (StAR) in six patients with congenital lipoid adrenal hyperplasia.
abstract: Congenital lipoid adrenal hyperplasia (lipoid CAH), the most severe form of CAH, is caused by mutations in the steroidogenic acute regulatory protein (StAR). Lipoid CAH is common among the Japanese, Korean, and Palestinian Arab populations, but is rare elsewhere. We describe six patients with lipoid CAH: four Japanese, one Palestinian, and one Guatemalan Native American. All had classical clinical presentations of normal female external genitalia in both genetic sexes, with severe glucocorticoid and mineralocorticoid deficiency presenting in the first month of life. Quite atypically, one patient had small adrenal glands shown by computed tomographic scanning. The StAR genes were characterized in all six patients. Three of the Japanese patients were compound heterozygotes for the common Japanese mutation Q258X in association with three different novel frameshift mutations; the fourth Japanese patient was homozygous for the mutation R182L, which is common among Palestinian patients but has not been described previously in a Japanese patient. Our Palestinian and Native American patients were each homozygous for novel frameshift mutations. Thus we have found five new frameshift mutations, but no new amino acid replacement (missense) mutations. This would be consistent with the view that only a small number of residues in the StAR protein are crucial for biological activity. The tomographic finding of small adrenals in a patient with genetically proven lipoid CAH due to a StAR mutation suggests a substantially broader spectrum of clinical findings in this disease than has been appreciated previously.
authors.affiliation: Department of Pediatrics and Metabolic Research Unit, University of California, San Francisco 94143-0978, USA.
authors.forename: H S
authors.initials: HS
authors.lastname: Bose
authors.forename: S
authors.initials: S
authors.lastname: Sato
authors.forename: J
authors.initials: J
authors.lastname: Aisenberg
authors.forename: S A
authors.initials: SA
authors.lastname: Shalev
authors.forename: N
authors.initials: N
authors.lastname: Matsuo
authors.forename: W L
authors.initials: WL
authors.lastname: Miller
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000483:Alleles; D000596:Amino Acids / Q000378:metabolism; D018912:Arabs; D005091:Exons / Q000235:genetics; D005260:Female; D006166:Guatemala; D006801:Humans; D007223:Infant; D007564:Japan; D007621:Karyotyping; D050356:Lipid Metabolism; D008055:Lipids / Q000235:genetics; D009154:Mutation / Q000235:genetics* / Q000502:physiology; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D000596:Amino Acids; D008055:Lipids; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein