Testing of NBIA Genes: Analysis of Genetic Heterogeneity and Validation of Mitochondrial Markers for Assessing Causality of Sequence Variants.

Neurodegeneration with brain iron accumulation (NBIA) represent a group of rare neurodevelopmental diseases, genetically as well as phenotypically heterogeneous.The diagnosis is based on brain MRI. It is also based on genetic testing. However overlaps exist between the different clinical presentations and the molecular diagnosis may be misinterpreted.Two main purposes must be addressed to get a better molecular diagnosis: on one hand reaching enough exhaustivity which may be performed with a larger gene panel and next generation sequencing; on the other hand, it is now necessary to validate or infirm the deleterious consequences of variants with the help of functional studies.

Inclusion Criteria:NBIA Patients diagnosed with a pathogenic variation or any variation that could impact gene function (class 4 or 5 according to ACMG criteria) in the following genes: C19ORF12, PANK2, PLA2G6, DCAF17, FA2H, WDR45, FTL, CP and ATP13A2 and whose fibroblasts have been collected at Bordeaux University Hospital for functional analysis during the diagnosis procedureNBIA patients without conclusive testing in none of these nine genes and whose DNA has been collected during the diagnosis procedure at Bordeaux University HospitalExclusion Criteria:Patients without imaging (MRI or scan) signs of NBIAPatients without french healthcare insurance