Hiort, O;
Holterhus, PM;
Werner, R;
Marschke, C;
Hoppe, U;
Partsch, CJ;
Riepe, FG;
... Struve, D; + view all
(2005)
Homozygous disruption of P450 side-chain cleavage (CYP11A1) is associated with prematurity, complete 46,XY sex reversal, and severe adrenal failure.
The Journal of Clinical Endocrinology & Metabolism
, 90
(1)
538 - 541.
10.1210/jc.2004-1059.
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Abstract
Disruption of the P450 side-chain cleavage cytochrome (P450scc) enzyme due to deleterious mutations of the CYP11A1 gene is thought to be incompatible with fetal survival because of impaired progesterone production by the fetoplacental unit. We present a 46, XY patient with a homozygous disruption of CYP11A1.The child was born prematurely with complete sex reversal and severe adrenal insufficiency. Laboratory data showed diminished or absent steroidogenesis in all pathways. Molecular genetic analysis of the CYP11A1 gene revealed a homozygous single nucleotide deletion leading to a premature termination at codon position 288. This mutation will delete highly conserved regions of the P450scc enzyme and thus is predicted to lead to a nonfunctional protein. Both healthy parents were heterozygous for this mutation.Our report demonstrates that severe disruption of P450scc can be compatible with survival in rare instances. Furthermore, defects in this enzyme are inherited in an autosomal-recessive fashion, and heterozygote carriers can be healthy and fertile. The possibility of P450scc-independent pathways of steroid synthesis in addition to the current concept of luteoplacental shift of progesterone synthesis in humans has to be questioned.
| Type: | Article |
|---|---|
| Title: | Homozygous disruption of P450 side-chain cleavage (CYP11A1) is associated with prematurity, complete 46,XY sex reversal, and severe adrenal failure |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1210/jc.2004-1059 |
| Publisher version: | http://dx.doi.org/10.1210/jc.2004-1059 |
| Language: | English |
| Additional information: | © 2005 by The Endocrine Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/us/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | ACUTE REGULATORY PROTEIN, GENE, HYPERPLASIA, SITE, CYTOCHROME-P450, INSUFFICIENCY, ADRENODOXIN, EXPRESSION, DESMOLASE, MUTATIONS |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/100469 |
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