scholarly journals Compound Heterozygous Mutations in the Cholesterol Side-Chain Cleavage Enzyme Gene (CYP11A) Cause Congenital Adrenal Insufficiency in Humans

2002 ◽  
Vol 87 (8) ◽  
pp. 3808-3813 ◽  
Author(s):  
Noriyuki Katsumata ◽  
Masatoshi Ohtake ◽  
Toru Hojo ◽  
Eishin Ogawa ◽  
Takayuki Hara ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Side Chain ◽  
Compound Heterozygous ◽  
Enzyme Gene ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Cleavage Enzyme ◽  
Compound Heterozygous Mutations

Heterozygous mutations in the cholesterol side-chain cleavage enzyme gene (CYP11A1) can cause transient adrenal insufficiency and life-threatening failure to thrive

HORMONES ◽  
2018 ◽  
Vol 17 (3) ◽  
pp. 419-421 ◽  
Author(s):  
Dimitrios T. Papadimitriou ◽  
Christina Bothou ◽  
Diagoras Zarganis ◽  
Maria Karantza ◽  
Anastasios Papadimitriou
Keyword(s):  
Adrenal Insufficiency ◽  
Failure To Thrive ◽  
Side Chain ◽  
Enzyme Gene ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Cleavage Enzyme ◽  
Life Threatening

scholarly journals Heterozygous Mutation in the Cholesterol Side Chain Cleavage Enzyme (P450scc) Gene in a Patient with 46,XY Sex Reversal and Adrenal Insufficiency

2001 ◽  
Vol 86 (8) ◽  
pp. 3820-3825 ◽  
Author(s):  
Toshihiro Tajima ◽  
Kenji Fujieda ◽  
Naoya Kouda ◽  
Jun Nakae ◽  
Walter L. Miller
Keyword(s):  
Adrenal Insufficiency ◽  
Cellular Damage ◽  
Dominant Negative Effect ◽  
Side Chain ◽  
Heterozygous Mutation ◽  
Adrenal Hyperplasia ◽  
Side Chain Cleavage ◽  
Congenital Lipoid Adrenal Hyperplasia ◽  
Chain Cleavage ◽  
Cleavage Enzyme

Cytochrome P450scc, the mitochondrial cholesterol side chain cleavage enzyme, is the only enzyme that catalyzes the conversion of cholesterol to pregnenolone and, thus, is required for the biosynthesis of all steroid hormones. Congenital lipoid adrenal hyperplasia is a severe disorder of steroidogenesis in which cholesterol accumulates within steroidogenic cells and the synthesis of all adrenal and gonadal steroids is impaired, hormonally suggesting a disorder in P450scc. However, congenital lipoid adrenal hyperplasia is caused by mutations in the steroidogenic acute regulatory protein StAR; it has been thought that P450scc mutations are incompatible with human term gestation, because P450scc is needed for placental biosynthesis of progesterone, which is required to maintain pregnancy. In studying patients with congenital lipoid adrenal hyperplasia, we identified an individual with normal StAR and SF-1 genes and a heterozygous mutation in P450scc. The mutation was found in multiple cell types, but neither parent carried the mutation, suggesting it arose de novo during meiosis, before fertilization. The patient was atypical for congenital lipoid adrenal hyperplasia, having survived for 4 yr without hormonal replacement before experiencing life-threatening adrenal insufficiency. The P450scc mutation, an in-frame insertion of Gly and Asp between Asp271 and Val272, was inserted into a catalytically active fusion protein of the P450scc system (H2N-P450scc-Adrenodoxin Reductase-Adrenodoxin-COOH), completely inactivating enzymatic activity. Cotransfection of wild-type and mutant vectors showed that the mutation did not exert a dominant negative effect. Because P450scc is normally a slow and inefficient enzyme, we propose that P450scc haploinsufficiency results in subnormal responses to ACTH, so that recurrent ACTH stimulation leads to a slow accumulation of adrenal cholesterol, eventually causing cellular damage. Thus, although homozygous absence of P450scc should be incompatible with term gestation, haploinsufficiency of P450scc causes a late-onset form of congenital lipoid adrenal hyperplasia that can be explained by the same two-hit model that has been validated for congenital lipoid adrenal hyperplasia caused by StAR deficiency.

P450 side-chain cleavage enzyme autoantibodies in canine Addison's disease

2013 ◽  
pp. 1-1
Author(s):  
Alisdair Boag ◽  
Kerry McLaughlin ◽  
Mike Christie ◽  
Peter Graham ◽  
Harriet Syme ◽  
...  
Keyword(s):  
Addison’S Disease ◽  
Side Chain ◽  
Addison's Disease ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Cleavage Enzyme

Comparison of the immunochemical properties of human placental and bovine adrenal cholesterol side-chain cleavage enzyme complex

1989 ◽  
Vol 998 (2) ◽  
pp. 189-195 ◽  
Author(s):  
Sergei A. Usanov ◽  
Paavo Honkakoski ◽  
Matti A. Lang ◽  
Markku Pasanen ◽  
Olavi Pelkonen ◽  
...  
Keyword(s):  
Side Chain ◽  
Enzyme Complex ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Cleavage Enzyme

scholarly journals Varied Clinical Presentations of Seven Patients With Mutations inCYP11A1Encoding the Cholesterol Side-Chain Cleavage Enzyme, P450scc

2013 ◽  
Vol 98 (2) ◽  
pp. 713-720 ◽  
Author(s):  
Meng Kian Tee ◽  
Michal Abramsohn ◽  
Neta Loewenthal ◽  
Mark Harris ◽  
Sudeep Siwach ◽  
...  
Keyword(s):  
Side Chain ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Clinical Presentations ◽  
Cleavage Enzyme
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