An international team of researchers has used ancient DNA to diagnose a rare genetic growth disorder in two individuals buried together over 12,000 years ago in southern Italy. The analysis reveals that the younger person suffered from acromesomelic dysplasia, while her likely mother had a milder form of short stature. This discovery highlights the deep history of rare genetic conditions in human populations.
In 1963, archaeologists discovered a double burial at Grotta del Romito in southern Italy, featuring two individuals from the Upper Paleolithic period, over 12,000 years ago. The skeletons, known as Romito 1 and Romito 2, showed unusual traits: Romito 2 had notably shortened limbs and stood about 110 cm tall, while Romito 1 measured roughly 145 cm. For decades, scientists debated their relationship, sex, and possible medical explanations for their statures.
Recent ancient DNA analysis, led by researchers from the University of Vienna and Liège University Hospital Centre, has clarified these questions. Extracted from the petrous bones of the skeletons, the genetic material confirmed that both were female and first-degree relatives, most likely mother and daughter. Romito 2 carried a homozygous mutation in the NPR2 gene, diagnosing acromesomelic dysplasia, Maroteaux type—a rare disorder causing severe short stature and limb shortening. Romito 1 had a single altered copy of the gene, associated with milder short stature.
The findings, published in the New England Journal of Medicine, demonstrate the power of paleogenomics in tracing genetic diseases back to prehistoric times. Ron Pinhasi of the University of Vienna 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."
Daniel Fernandes of the University of Coimbra added, "Identifying both individuals as female and closely related turns this burial into a familial genetic case. The older woman's milder short stature likely reflects a heterozygous mutation, showing how the same gene affected members of a prehistoric family differently."
Adrian Daly of Liège University Hospital Centre noted, "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 her condition, Romito 2 survived into adolescence or adulthood, suggesting community support. Alfredo Coppa of Sapienza University of Rome remarked, "We believe her survival would have required sustained support from her group, including help with food and mobility in a challenging environment."