Oldest clinical case of a rare genetic condition discovered

A group of international researchers including experts from the University of Adelaide has uncovered evidence of a genetic condition that gives men an extra X chromosome, reporting the oldest clinical case of Klinefelter Syndrome to date.

The team analysed genetic information obtained from a skeleton found in northeastern Portugal that had been radiocarbon dated to the 11th century by researchers from the University of Coimbra in Portugal.

DNA was analysed at the University of Adelaide’s Australian Centre for Ancient DNA (ACAD).

Associate Professor Bastien Llamas, Head of Molecular Anthropology at ACAD, said: “In recent years, ancient DNA helped rewrite the history of worldwide human populations. Our study demonstrates it is now a valuable resource for biomedical research and the growing field of evolutionary medicine.”

PhD student at the University of Adelaide, Xavier Roca-Rada, extracted the DNA at ACAD’s ultra-clean laboratory facilities using strict protocols adapted to the minute quantities of fragmented and contaminated DNA.

“Genetic analysis was undertaken to computationally map the degraded DNA fragments of the X and Y chromosomes to the reference human genome”.

Klinefelter Syndrome is a genetic condition where male individuals are born with an extra copy of the X chromosome, occurring in approximately one in 1,000 genetic-male births.

The study coordinated by Dr João Teixeira, an ARC DECRA Fellow at The Australian National University (ANU) and a titleholder with the University of Adelaide, brought together an international and multidisciplinary team that combined genetic, statistical, archaeological and anthropological information to establish a definitive diagnosis.

“Given the fragile state of the DNA, we developed a new statistical method that could take into account the characteristics of ancient DNA, and our observations to confirm the diagnosis,” Dr Teixeira said.

“In recent years, ancient DNA helped rewrite the history of worldwide human populations. Our study demonstrates it is now a valuable resource for biomedical research and the growing field of evolutionary medicine.”Associate Professor Bastien Llamas, Head of Molecular Anthropology at the University of Adelaide’s Australian Centre for Ancient DNA (ACAD).

Given the relatively good preservation of the specimen, the researchers were also able to determine physical traits in the skeleton compatible with Klinefelter Syndrome.

“We were immediately excited the first time we looked at the results,” Dr Teixeira said. “However, ancient DNA is often degraded and of low quality and abundance, meaning we were initially cautious.”

The researchers say the findings will help establish a historic record for Klinefelter Syndrome, as well as enhance understanding of its prevalence throughout human history.

“Our research shows the immense potential of combining different lines of evidence to study the human past, and the frequency of different health conditions through time,” Dr Teixeira said.

“While the study offers compelling evidence for the genetic history of Klinefelter Syndrome, no sociological implications can be drawn from this diagnostic.”

The researchers suggest their new statistical method to analyse the genetic data can be further improved to study different chromosomal abnormalities, including Down Syndrome, in other archaeological specimens but also in forensics and pre-natal diagnosis settings.

This research is published in The Lancet.