Rare genetic syndrome discovered in Emirati boy helps identify symptoms across Middle East

An Emirati father's determination to find out what was causing his son's constant illness has led to the discovery of a rare genetic syndrome in the Middle East . Majid Salim Muhammad Saif Al Shamili, from Ras Al Khaimah , said Salem was repeatedly taken to hospital with infections, often choking and experiencing "very slow growth". Other symptoms included delays in neurodevelopment, and abnormalities in the shape of his head and face. It was only after Salem, five, was seen at the Al Jalila Children’s Hospital in Dubai that an endocrinology specialist, Dr Nandu Thalange, suspected a genetic change may have been responsible and he instructed a detailed analysis be carried out. Along with his colleagues, Dr Ahmad Abou Tayoun, director of the Dubai Health Genomic Medicine Centre and an associate professor of genetics at Mohammed Bin Rashid University, found the child had a condition caused by a single gene mutation. When Salem was first taken to hospital in 2020, it kick-started a major research project that led to the identification of more than a dozen children from the UAE, and elsewhere in the region, who were also found to have the disease. “My reaction at the beginning when he was diagnosed was very difficult for us as his parents, and also my son was the first case of this disease [in the region], so this is what worried us,” said Mr Al Shamili. After a study, which took five years to complete, researchers have released their findings to identify and characterise the condition, which has so far been seen only in Arab children but which may also affect people from other parts of the world. "Although we saw the first patient back in 2020, we really didn't confirm the diagnosis until the conclusion of the study and [after] evaluating all of the data," said Dr Tayoun, co-author of the paper published in the American Journal of Human Genetics . Salem had inherited a mutation from each parent, which made him unable to produce a vital protein in his cells, leading to changes that caused his symptoms. "We realised this was the most likely cause of disease and submitted our findings to an online tool where investigators worldwide submit novel genes they identified in undiagnosed patients,” Dr Tayoun said. Based on the symptoms and the gene, the tool matched the Dubai researchers with a geneticist in Saudi Arabia, Dr Bruno Reversade, and researchers in Germany who had analysed DNA samples from Middle Eastern patients. With the study under way, another patient at Al Jalila Children’s Hospital was found to have the same genetic variant, known as FBX022. "Other similarly affected patients were also identified in the GCC and Lebanon,” said Dr Tayoun – a total 16 patients who had similar symptoms and shared mutations in the gene were identified. Much of the genetic work was undertaken at the Dubai Health Genomic Medicine Centre, which was previously known as the Genomic Centre of Excellence at Al Jalila Children's Specialty Hospital. “Doing genomics work locally is crucial for research activities and discoveries like this one,” Dr Tayoun said. He said the work also showed Dubai Health’s commitment to “advancing medical discovery” by involving clinicians, clinical scientists and researchers. “This work also highlights the importance of regional and international collaborations, given the rarity of monogenic diseases [caused by a mutation to a single gene] and the need to connect similarly affected patients to establish causality,” he said. The analysis indicates that the most common variant of FBX022 identified probably originated in the Middle East, so it is more common in the region than elsewhere. The research identified seven affected Emirati families, all having the most common variant, as did all four families from Oman. Families from Saudi Arabia and Lebanon had different variants. “All patients so far identified are Arabs but we are sure, now the gene has been discovered, that patients from other populations will be identified, though with different variants,” Dr Tayoun said. It is possible children may have had the condition in the past but the cause of their symptoms went unrecognised, he added. Being a newly identified syndrome, there is not yet any treatment for the condition. The most effective approach, should it be possible, would be a form of therapy in which the deficient form of the gene is replaced with a normal copy. Dr Tayoun said this replacement would need to be done in time to avoid “irreversible, permanent changes during development”. The Middle East tended to be under-represented in global genomic studies, Dr Tayoun said, resulting in “missed opportunities” to identify novel genetic conditions specific to the region. While a cure is not possible, Salem, who turns six next month, is showing “very good” development compared to his first three years, his father said, and medication is controlling symptoms such as spasms. His cognition has improved and is continuing to develop thanks to the treatment. “Now he is undergoing physical and occupational therapy and, thank God, he has started to develop and acquire skills, such as standing and walking a little,” said Mr Al Shamili.

Rare genetic syndrome discovered in Emirati boy helps identify symptoms across Middle East

Condition causes slower growth and abnormalities in the head and face