Sidra Medicine, a member of Qatar Foundation, has contributed to a study that uncovers new genetic causes and disease mechanisms behind Ritscher-Schinzel Syndrome (RSS), a rare multi-system congenital disorder.

The study, published in Science Translational Medicine, is one of the first from the region to identify the genetic basis of RSS, marking a significant advancement in the global understanding of this condition.

Titled “Ritscher-Schinzel syndrome can be characterized as an endosomal recyclinopathy,” the study was led by researchers from Sidra Medicine, the University of Bristol, and leading academic and clinical institutions across Japan, the Netherlands, and Egypt.

Dr Aljazi al-Maraghi, staff scientist at Sidra Medicine said: “This research revealed multiple novel disease-causing genes in patients with RSS and uncovered how disruptions in a critical cellular system, known as the Commander complex, which is responsible for recycling proteins within cells, can lead to disease. When this system fails, essential proteins don’t reach the organs where they’re needed, resulting in impaired development of the brain, kidneys, and bones. Our joint efforts will help accelerate progress in understanding rare diseases laying the groundwork for the future development of therapeutic strategies.”

Researchers studied newly identified patient groups, including three siblings from a consanguineous Arab family enrolled in Sidra Medicine’s Mendelian and Metabolic disorders Translational Research Programme. As a result of their collaboration, RSS is now recognised as a 'recyclinopathy,' a disorder caused by defects in cellular recycling.

Prof Khalid Fakhro, chief research officer and chair of the Precision Medicine Programme at Sidra Medicine, said: "This study demonstrates how our Mendelian and Metabolic disorders Programme is transforming the landscape of genetic research and diagnosis in the region. By investigating families with rare conditions, particularly in communities with high rates of consanguinity, we are uncovering novel disease genes and mechanisms that were previously unknown.”

The study used genetic, cellular, proteomic, and animal model approaches to uncover how mutations in three genes, COMMD4, COMMD9, and CCDC93, are linked to RSS.

Dr Ammira Akil, programme director of the Mendelian and Metabolic Disorders at Sidra Medicine said: “By uniting diverse expertise in genetics, cell biology, pediatric care, and in close collaboration with clinicians at Sidra Medicine within the programme, the team was able to contribute to uncover the genetic underpinnings of RSS. The discovery highlights how contributions from consanguineous families are helping scientists bridge the gap between gene discovery and real-world impact.”

Prof Kohji Kato, research associate at the University of Bristol added: “We truly hope these findings will help improve the quality of care for affected patients. Looking ahead, we are eager to work toward developing effective treatments as well.”