Sexual Developmental Disorder Linked to Closed 'Back Door' Pathway

Scientists in Switzerland have found that a sexual developmental disorder in baby boys may be due to the absence of a hormone-production pathway identified in wallabies.

The finding could help diagnose cases of ambiguous genitalia, New Scientist reported.

One in 4500 babies has gene mutations that disrupt normal development of testes or ovaries in the womb. These children can be born with external genitalia that do not look typically female or male.

In humans, normal development of the testes relies on two male hormones - testosterone and dihydrotestosterone (DHT). The latter is the more potent, and is produced when testosterone is broken down.

Wallabies and some rodents are known to be able to make DHT via two different routes, one of which bypasses testosterone completely. The process works by converting cholesterol, the precursor to testosterone, directly into DHT.

To find out whether a similar "back door" pathway exists in humans, Anna Biason-Lauber and her colleagues at the University Children's Hospital Zurich in Switzerland investigated the genetic make-up of a family, three of whom have ambiguous genitalia.

As these individuals were all able to produce DHT from testosterone, multiple attempts to diagnose the cause of their symptoms had failed.

Biason-Lauber's team screened all the family members for mutations in four genes - AKR1C1 to AKR1C4 - known to be involved in producing DHT from cholesterol in the wallaby.

They found that two of the genes were mutated only in the three affected individuals, suggesting they were unable to make DHT using this pathway.

Further screening of 34 people with similar disorders revealed a mutation in one of these genes in four of them.

"This unique, newly described form of developmental sexual disorders establishes that the back door pathway is essential for normal male sexual development," said Biason-Lauber.

Source: ANI