Oldest case of Klinefelter syndrome diagnosed in ancient skeleton

A multidisciplinary team of researchers has discovered what is believed to be the oldest case of Klinefelter syndrome in a 1,000-year-old skeleton. The finding is described in a new study published in The Lancet.

What is Klinefelter syndrome?

DNA, the “blueprint” that encodes proteins needed for biological functions, is efficiently packaged within a cell’s nucleus, tightly wrapped around proteins called histones. These DNA threads are organized into chromosomes, inherited from our parents – 23 from our mother and 23 from our father. The 23rd pair of chromosomes are known as the “sex chromosomes” because they determine whether an individual is born male or female. Individuals assigned female at birth inherit two X chromosomes, while those assigned male at birth inherit one X chromosome and one Y chromosome.

Klinefelter syndrome is a genetic disorder that occurs when a male is born with an extra copy of the X chromosome, affecting approximately 1 in 1,000 people. Symptoms of Klinefelter syndrome may include growth and development delays and/or fertility problems and a low libido. Diagnosis is often made using hormone tests and chromosome analysis (or karyotyping) to study the shape and number of chromosomes.

Oldest known case of Klinefelter syndrome

By analyzing ancient DNA, Dr Joao TeixeiraARC DECRA Fellow at the Australian National University (ANU) and his colleagues recently discovered what is believed to be the oldest case of Klinefelter syndrome.

A skeleton discovered in the medieval archaeological site of Torre Velha in northeastern Portugal has been radiocarbon dated to the 11e century by scientists from the University of Coimbra, Portugal. The skeleton – an adult male, aged 25 at the time of death – was sent to the Australian research team for genetic analysis.

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

To overcome the limitations typically associated with analyzing ancient DNA from osteological remains, the research team developed a new Bayesian method that they “believe is a potentially effective statistical way to analyze fragmented DNA.” from a variety of sources (e.g., ancient DNA, cell-free DNA, and forensic case DNA)”, they write in the paper.

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

DNA was extracted from the remains and genetically analyzed to map degraded DNA fragments from the X and Y chromosomes against the reference human genome. Combining their analyzes using the new method, the researchers concluded that the individual’s karyotype was 47 XXY, meaning he carried an extra X chromosome. As the individual’s skeleton was well preserved, Teixeira and his colleagues were also able to study his physical features, which were consistent with the diagnosis of Klinefelter syndrome (taller height than the average ancient Portuguese man, greater bi-iliac width and jaw malocclusion and maxillary prognathism).

“In recent years, ancient DNA has helped rewrite the history of human populations around the world. Our study demonstrates that it is now a valuable resource for biomedical research and the burgeoning field of evolutionary medicine,” said Dr Bastien Llamas, associate professor and head of molecular anthropology at the Australian Center for Ancient DNA, said.

Reference: Roca-Rada X, Tereso S, Rohrlach AB, et al. A 1000-year-old case of Klinefelter syndrome diagnosed by integrating morphology, osteology and genetics. The Lancet. 2022;400(10353):691-692. do I: 10.1016/S0140-6736(22)01476-3.

This article is a reprint of a Press release issued by the Australian National University. Material has been edited for length and content.

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