Cognitive impairment and mental retardation in children: Key new mechanisms of brain development identified

Researchers from the University of Genoa and the Giannina Gaslini Institute in collaboration with the Aichi Center for Developmental Disabilities, using the latest genetic sequencing technology, have identified mutations in the RAC3 gene in all patients. The study was published in Brain .

Genoa, April 26, 2022 – Researchers from the University of Genoa and the IRCCS Istituto Giannina Gaslini in collaboration with the Aichi Center for Developmental Disabilities (Japan) have identified new mechanisms underlying the development and functioning of the human brain. The resulting work was published in the latest issue of the journal brain.

The research was conducted by Marcello Scala, UBC Pediatric Doctor of Neurology and Musculoskeletal Student of the IRCCS Istituto Giannina Gaslini and Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Science (DINOGMI) University of Genoa, in collaboration with Masashi Nishikawa and under the supervision of Kohichi. Nagata.

Dr. Marcelo Scala

The study was led by Dr. Pascual Striano of the University of California Pediatric Neurology and Musculoskeletal in Gaslini and Dr. Valeria Capra, a geneticist from the University of Oklahoma in Gaslini. Co-author of the international collaboration, the Department of Molecular Neurobiology at the Center for Developmental Disabilities in Aichi under the direction of Kohichi Nagata is already the author of several prestigious papers on brain development and the mechanisms by which neurons form the cerebral cortex in humans.

The study also saw related collaboration with the Telethon Project: Diseases without Diagnostics, coordinated by Vincenzo Nigro at TIGEM in Naples.

The participating researchers studied a group of children from various Italian and international centers (Australia, Belgium, Canada, Germany, France, Spain, Turkey and the USA), with intellectual developmental disorder, epilepsy and complex malformations of the brain and cerebellum.

Using the latest generation of genetic sequencing technology, mutations in the RAC3 gene were identified in all patients. This gene encodes a protein necessary for the assembly of the skeleton of neurons, and, accordingly, for their functioning. Studying the effects of these mutations through improved molecular biology techniques has shown that diseased neurons are unable to acquire an adult form and do not migrate properly to the cerebral cortex during brain development.

“This research – declares Pasquale Striano, new director of the University of California in Pediatric Neurology and Musculoskeletal at Gaslini – is the result of multiple international collaborations between our institute and the University of Genoa with important international research centers and in particular with the Nagata team at the Aichi Developmental Disability Center. The study provides answers important on some of the many and complex questions relating to the origins of neurodevelopmental disorders in children, and offers interesting future perspectives in both potential diagnostic and therapeutic areas.

“From the findings of this study – adds Federico Zara, UOC Director of Medical Genetics at Gaslini – important implications can be derived for a better understanding of the mechanisms by which the human brain is formed and, from a perspective perspective, potential normative mechanisms for improving prognosis and quality of life for patients with of neurodevelopmental disorders.

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