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Understanding the basis of cerebellar and brainstem congenital defects: from clinical and molecular characterisation to the development of a novel neuroembryonic in vitro model


Cerebellar and brainstem congenital defects (CBCDs) are heterogeneous disorders with high pre-and post-natal mortality and morbidity. Their genetic basis and pathogenetic mechanisms are largely unknown, hampering patients’ diagnosis and management and family counselling. This project aims at improve current understanding of primary CBCDs through a multidisciplinary approach combining innovative clinical, neuroimaging, molecular and functional studies, that will be articulated in four workpackages:
WP1- Clinical and neuroimaging studies: collection of detailed data and biological samples from a large cohort of patients covering a broad spectrum of CBCDs, neuroimaging classification based on magnetic resonance imaging and tractography, genotype-phenotype correlates and follow-up studies.
WP2 - Molecular studies on mendelian CBCDs: high-throughput resequencing of ciliary genes to identify pathogenic mutations and genetic modifiers in patients with ciliopathies, identification of novel disease genes, mutation analysis of genes causative of other mendelian CBCDs.
WP3 - Molecular studies on sporadic CBCDs: identification of cryptic chromosomal rearrangements by high resolution SNP-array analysis, selection and mutation analysis of candidate genes mapping to the rearranged regions.
WP4 - Functional studies: optimisation of a novel neuroembryonic in vitro model derived from mouse embryonic stem cells, to test the role of known and candidate disease genes (from WP2 and 3) on cerebellar and brainstem development, define the pathways in which they are involved and the effect of disease-causative mutations.
This project is expected to improve the current CBCD nosology, identify novel genes and mechanisms involved in cerebellar and brainstem development that are responsible for mendelian or sporadic defects, expand the available tools for pre- and post-natal diagnosis and identify clinical-genetic correlates and prognostic indexes.

Call for proposal

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Strada nuova 65
27100 Pavia

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Nord-Ovest Lombardia Pavia
Activity type
Higher or Secondary Education Establishments
Principal investigator
Enza Maria Valente (Prof.)
Administrative Contact
Sofia Baggini (Dr.)
EU contribution
No data

Beneficiaries (3)