UCL study identifies new clinical syndrome
7 May 2009
UCL scientists have discovered a hitherto unknown clinical syndrome - now named EAST syndrome - in patients by identifying its underlying genetic mutation.
The study, published in the current edition of the New England Journal of Medicine (NEMJ), delineates that a mutation in the gene KCNJ10, the key regulator of salt transport in the kidney, causes a previously unrecognised disease which begins in infancy and that affects the kidney, brain and ear.
The patients - all in long-term care - presented symptoms of epilepsy; ataxia (movement disorder); senorineural deafness; and tubulopathy (electrolyte disorder due to kidney involvement). The research team, led by Professor Robert Kleta (UCL Medicine) and Dr Detlef Bockenhauer (UCL Institute of Child Health), was able to pinpoint the cause of all these problems to a single gene by studying a family affected by these conditions.
Dr. Bockenhauer commented: "To offer a diagnosis to patients, parents and colleagues is a huge step forward. Our findings will obviate the need for unnecessary studies in patients affected by EAST syndrome. They will make genetic counselling feasible and allow us to learn more about the clinical development and prognosis, which in turn will improve their care. Moreover, the insights provided by studying patients with rare disorders have important implications for many other patients.
"The function of the potassium channel gene we discovered being mutated in EAST syndrome has implications for electrolyte (sodium, potassium, calcium, magnesium) and also water transport in brain, the inner ear and in the kidney. Consequently, this gene is linked to hypertension and epilepsy. Our new knowledge can therefore help to advance the care of these common disorders. For instance, we are now working on trying to understand the seizure disorder in more detail since epilepsy still presents a challenge in daily clinical practice with respect to diagnosis and treatment."
The study included collaboration with international scientists from the US, Germany, Israel, United Arab Emirates and Mali. Researchers now possess vital evidence which will inform future treatment strategies not only for patients with EAST syndrome, but also for more common disorders that affect these organs, such as hypertension or epilepsy.
Professor Kleta added: "Our work was possible thanks to clinicians who collaborated closely with each other across UCL campuses and hospitals. Collaborations between NHS clinicians and UCL scientists worked out very well for the benefit of the patients. Furthermore, a strong collaboration with UCL Genomics under the lead of Dr. Mike Hubank at the Institute of Child Health (ICH) has enabled our group to build up analytical methods to interpret genetic data rather quickly."
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