EUROMICRO

Primary Microcephalies (PMs) are rare heterogeneous disorders resulting from insufficient production of mature neurons. Known causal genes are involved in cell-cycle control, DNA integrity, centrosome and spindle pole organization. Alterations to these processes may lead to isolated PM (MCPH) or PM with dwarfism (Seckel syndrome, microcephalic osteodysplastic primordial dwarfism type 2, Meier-Gorlin syndrome). Causal genes are currently known in 30-50% of patients. In this project, named EuroMicro, 5 teams with extensive experience with PM join forces to gain insights into the natural history of the disease and its underlying mechanisms, which involve basic processes in brain development. The ultimate aim is to improve patient care and become a clinical and scientific resource center for patients with PM in Europe. EuroMicro is divided into 5 work packages: 1) to collect clinical data, genetic data and biological samples from patients with PM and to bank all these data in a common web-based database 2) to explore the molecular mechanisms underlying PM by identifying new PM genes 3) to explore the pathophysiology of PM by studying the cellular and neuropathological phenotypes caused by mutations in PM genes 4) to elucidate defects in neurogenesis using human induced pluripotent stem cells derived from PM patients 5) to characterize patients at the clinical level (natural history, comorbidities, brain imaging, impact of mutations on cognitive functioning and social behavior), in order to detect specific cognitive disabilities and propose suitable remediation strategies.