Abstract | CONTEXT: OBJECTIVE: We describe two siblings with hormonal findings suggesting nonclassic lipoid CAH, who had a P450scc mutation that retains partial function. PATIENTS AND METHODS: A 46,XY male presented with underdeveloped genitalia and partial adrenal insufficiency; his 46,XX sister presented with adrenal insufficiency. Hormonal studies suggested nonclassic lipoid CAH. Sequencing of the StAR gene was normal, but compound heterozygous mutations were found in the CYP11A1 gene. Mutations were recreated in the F2 plasmid expressing a fusion protein of the cholesterol side-chain cleavage system. P450scc activity was measured as Vmax/Km for pregnenolone production in transfected COS-1 cells. RESULTS: The patients were compound heterozygous for the previously described frameshift mutation 835delA and the novel missense mutation A269V. When expressed in the P450scc moiety of F2, the A269V mutant retained 11% activity of the wild-type F2 protein. CONCLUSIONS: There is a broad clinical spectrum of P450scc deficiency. Partial loss-of-function CYP11A1 mutation can present with a hormonal phenotype indistinguishable from nonclassic lipoid CAH.
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Authors | Taninee Sahakitrungruang, Meng Kian Tee, Piers R Blackett, Walter L Miller |
Journal | The Journal of clinical endocrinology and metabolism
(J Clin Endocrinol Metab)
Vol. 96
Issue 3
Pg. 792-8
(Mar 2011)
ISSN: 1945-7197 [Electronic] United States |
PMID | 21159840
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents
- DNA
- Cholesterol Side-Chain Cleavage Enzyme
- Hydrocortisone
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Topics |
- Adrenal Hyperplasia, Congenital
(drug therapy, genetics, metabolism)
- Amino Acid Sequence
- Animals
- Anti-Inflammatory Agents
(therapeutic use)
- COS Cells
- Cell Line
- Child
- Child, Preschool
- Chlorocebus aethiops
- Cholesterol Side-Chain Cleavage Enzyme
(genetics, metabolism)
- Cryptorchidism
(genetics, metabolism)
- DNA
(genetics)
- DNA Mutational Analysis
- Female
- Frameshift Mutation
- Genetic Vectors
- Gonadal Dysgenesis, 46,XX
(genetics)
- Gonadal Dysgenesis, 46,XY
(genetics)
- Humans
- Hydrocortisone
(therapeutic use)
- Kinetics
- Male
- Molecular Sequence Data
- Mutation
(genetics, physiology)
- Mutation, Missense
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