What gene change causes Antley-Bixler syndrome?
There are two genetically distinct forms of Antley-Bixler syndrome (ABS). ABS with genital anomalies and disordered steroidogenesis is caused by changes (mutations) to the POR gene, which encodes instructions to make the enzyme cytochrome P450 oxidoreductase. This enzyme is important in the formation of steroid hormones, such as testosterone and estrogen. Changes to the POR gene decreases activity of the cytochrome P450 oxidoreductase leading to the disruption of steroid hormone production. Consequently, sexual development problems occur before birth and at puberty.
The enzyme cytochrome P450 oxidoreductase also plays a role in cholesterol production; which is also needed in the production of steroid hormones and in bone formation and growth. Disruptions in the POR gene can cause abnormal bone growth and fusion of bones.
The alternative form; ABS without genital anomalies and disordered steroidogenesis, is caused by changes to the FGFR2 gene, which provides instructions to make a protein called fibroblast growth factor receptor 2. This protein is involved in many biological processes, especially during embryonic development. For example, it plays a role in cell division, regulation of cell growth and maturation, and formation of blood vessels. It also contributes to bone growth by signalling cells in the developing embryo to become bones cells. Changes to the FGFR2 gene can cause increased signalling by FGFR2 protein, which causes premature closure of the bones in the skull.
Learn more about how the POR and FGFR2 gene works by visiting the Genetics Home Reference
Cytochrome P450 oxidoreductase deficiency - Genetics Home Reference - NIH. (n.d.). Retrieved December 25, 2018, from https://ghr.nlm.nih.gov/condition/cytochrome-p450-oxidoreductase-deficiency#statistics
FGFR2 gene - Genetics Home Reference - NIH. (n.d.). Retrieved December 25, 2018, from https://ghr.nlm.nih.gov/gene/FGFR2#conditions