The genetic cause of a rare skin cancer syndrome, Bazex–Dupré–Christol syndrome

Bazex–Dupré–Christol syndrome (BDCS) is a rare genetic skin condition characterized by poor hair growth, prominent hair follicle openings, especially on the backs of the hands, and multiple skin tumours, particularly basal cell carcinomas (BCCs). BDCS is an X-linked dominant condition, which means an affected father would pass on the condition to his daughters but not his sons, whereas an affected mother has a 50% chance of passing on the condition to both her sons and daughters. Previous studies have identified an area on the long arm of the X chromosome called Xq25-q27·1. It contains the gene ACTRT1, which is suspected to cause BDCS.

In this study, an international research team investigated the genetic cause of BDCS in eight families with the condition.

They found that all affected individuals had an abnormal, duplicated stretch of DNA on the long arm of the X chromosome. It was of different length in different individuals, but a short segment, Xq26·1, was common in all, making this a likely location for the gene causing BDCS. The previously suspected gene ACTRT1 is actually outside this segment, and further tests in these families excluded ACTRT1 as the cause of BDCS.

The Xq26·1 segment did not contain any genes that code for proteins. However, this duplication can disrupt interactions between other factors, leading to malfunction of nearby genes. A gene called ARHGAP36 was found at one end of the duplicated stretch and was prominent in hair follicles and BCCs from patients with BDCS. It was also detected in BCCs from individuals without BDCS.

The authors concluded that malfunction of ARHGAP36 is likely to be the cause of BDCS and of some BCCs in otherwise healthy people. This finding may help with genetic counselling and may suggest new approaches to treatment for both BDCS and BCCs.