An international team of researchers have unlocked the genetic cause of DOORS syndrome, paving the way for more accurate and timely diagnosis of this rare disease.
DOORS syndrome is a rare, autosomal recessive genetic condition characterised by deafness, onychodystrophy, osteodystrophy, intellectual disability and seizures.
BRC supported Professor Sanjay Sisodiya, a UCLH consultant neurologist and joint principal author of the study said: “The motivation for the study came from seeing patients with complex epilepsies referred under the NHS to our specialist UCLH clinical practice at Chalfont, headquarters of the Epilepsy Society, where a large proportion of referrals clearly have syndromes we generally don’t recognise and are undiagnosed”. Professor Sisodiya added: “It seemed possible that we should be able to pin this particular condition down genetically.”
The study, published in Lancet Neurology, recruited participants from 26 centres in 17 countries and used whole exome sequencing which revealed that mutations in the TBC1D24 gene are an important cause of DOORS syndrome.
Whole exome sequencing is an efficient and comparatively inexpensive alternative to whole genome sequencing that looks at exons, the protein-coding regions of genes.
Professor Sisodiya said: “This study is another demonstration that the cause of rare conditions like DOORS can be identified. Mutations in this gene were known to cause some other rare epilepsies, but one would not necessarily have suspected this gene in DOORS. Mutations in TBC1D24 seem able to cause a broad spectrum of conditions. There are clear implications for clinical practice relating to more accurate diagnosis, and for the value of exome sequencing in particular.”
To read ‘The genetic basis of DOORS syndrome: an exome-sequencing study’ in full click here.
