JOURNAL ARTICLE

A novel splicing junction mutation in the gene for the steroidogenic acute regulatory protein causes congenital lipoid adrenal hyperplasia

E Okuyama, N Nishi, S Onishi, S Itoh, Y Ishii, H Miyanaka, K Fujita, Y Ichikawa
Journal of Clinical Endocrinology and Metabolism 1997, 82 (7): 2337-42
9215316
Congenital lipoid adrenal hyperplasia (lipoid CAH) is a relatively common genetic disorder of adrenal and gonadal steroidogenesis and is the most severe form of CAH. As typical affected individuals cannot produce any steroid hormones or can only produce low levels of steroid hormones in the adrenals and gonads, including glucocorticoids, mineralcorticoids, and sex steroids, a genetic defect in the cholesterol side-chain cleavage enzyme, cytochrome P450scc (CYPXIA1), has been postulated to be the cause of their insufficient production to date. Recently, Lin and co-workers proved a link between mutations of the steroidogenic acute regulatory protein (StAR) gene and the lipoid CAH phenotype. Therefore, we investigated both the cytochrome P450scc and StAR genes in a Korean family with a fairly mild form of lipoid CAH to identify the mutation(s) causing this disease. The result was that no mutations could be found in the two genes, except for a thymine (T) insertion into intron 2 of the StAR gene, 3 bp from the splice donor site of exon 2. PCR-amplified StAR genes from a normal subject and the patient were cloned into an expression vector and then introduced into COS-7 cells. Northern blot and reverse transcriptase-PCR analyses indicated that the StAR messenger ribonucleic acid derived from the vector with the normal StAR gene spliced exons 2 and 3 correctly, whereas most, but not all, StAR messenger ribonucleic acid derived from the vector with the T-inserted StAR gene could not remove intron 2. We concluded from these results that the T insertion into the StAR gene accounts for the lipoid CAH phenotype in this patient.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read
9215316
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"