Researchers from the University of Vienna and Liège University Hospital Centre have identified genetic variants linked to a rare inherited growth disorder in two prehistoric individuals who lived over 12,000 years ago. The study, published in the New England Journal of Medicine, combined ancient DNA analysis with modern clinical genetics to diagnose the condition in a mother and daughter buried together in southern Italy.
The research focused on an Upper Paleolithic burial discovered in 1963 at Grotta del Romito, southern Italy. This burial has long been notable for its unusual skeletal features and the positioning of two individuals interred together. "Romito 2," previously thought to be male, was an adolescent with significant limb shortening, lying in the arms of "Romito 1," believed to be an adult female. Both individuals showed no signs of trauma but were shorter than average for their era.
Ancient DNA was extracted from the petrous part of the temporal bone—an area known for good preservation of genetic material. Genetic analysis confirmed that both individuals were female and first-degree relatives, most likely mother and daughter. The researchers screened genes associated with skeletal growth and compared these findings with modern clinical data.
The results revealed that Romito 2 had a homozygous variant in the NPR2 gene, which is essential for bone growth. This established a diagnosis of acromesomelic dysplasia, Maroteaux type—a rare inherited disorder characterized by severe short stature and pronounced limb shortening. Romito 1 carried one altered copy of the same gene, which is linked to milder short stature.
Ron Pinhasi from the University of Vienna, co-leader of the study, stated: "By applying ancient DNA analysis, we can now identify specific mutations in prehistoric individuals. This helps establish how far back rare genetic conditions existed and may also uncover previously unknown variants."
Adrian Daly from Liège University Hospital Centre added: "Rare genetic diseases are not a modern phenomenon but have been present throughout human history. Understanding their history may help recognising such conditions today."
Despite significant physical limitations due to her condition, Romito 2 survived into adolescence or adulthood. Alfredo Coppa from Sapienza University of Rome commented: "We believe her survival would have required sustained support from her group, including help with food and mobility in a challenging environment."
