It was an encounter with a little girl who suffered from an enigmatic neurological disorder that set molecular geneticist Huda Zoghbi on a journey of unexpected scientific discovery, taking her from the paediatric clinic to a medical laboratory, where she would unravel the genetic origins of a rare and devastating condition Rett Syndrome.

Professor Zoghbi, now Professor of Paediatrics, Neurology, Molecular and Human Genetics and Neuroscience at the Baylor College of Medicine, spoke on Monday of the significance of her days as a clinician when she was able to catch medical clues to the relatively unknown disease, and the promise of a treatment made possible by genome sequencing, which can today help identify the cause of several disorders.

It was 16 years after she met her first patient at the Texas Medical Centre in 1983 that she discovered a genetic mutation linked to Rett Syndrome, which caused a critical reduction of the methyl-CpG-binding protein 2 (MECP2) and affected every part and every function of the brain, Professor Zoghbi said in a lecture A journey from the clinic to the laboratory to understand brain disorders she delivered as part of the Cell Press-TNQ India Distinguished Lectureship Series.

Rett Syndrome, an autism spectrum disorder that primarily affects girls (1 in 10,000), alters no fewer than 2,500 genes, causing learning and memory deficits, motor dysfunction and sometimes convulsions. And curiously, this hereditary condition sets in six to 18 months into the childs life: The girl who would sing along to nursery rhymes and greet her father when he returned from work fell silent at the age of two years. She lost her ability to use her hands and would rarely make eye contact. She could not walk with ease and most strikingly, would wring her hands constantly, she said.

However, the techniques of genome sequencing have transformed diagnosis, allowing us to identify causes of so many disorders, said Professor Zoghbi, whose investigations have provided vital clues to the genetic and molecular mechanisms of other neurological disorders such as Spinocerebellar ataxia type 1 and Huntingtons disease.

We are at a time when we can contemplate therapies, she said, adding studies were under way to find out if an anti-epileptic drug can pharmacologically reverse some of the crippling symptoms. Years of research on mice models revealed that when MECP2 was not at its optimal level it impacted a specific class of neurons (GABAergic neurons), which could become targets for therapy to rescue MECP2 levels and therefore alleviate symptoms, she said.

Professor Zoghbi will deliver her lecture at the Music Academy in Chennai at 4.30 p.m., Wednesday, and at the Teen Murti Auditorium in New Delhi at 4.30 p.m. on Friday.

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Molecular geneticist Zoghbi throws light on enigmatic neurological disorder