French researchers report the exceptional case of a foetus suffering from a deficiency in mitofusin 2, a mitochondrial protein encoded by the MFN2 gene already implicated in autosomal, dominant or recessive forms of Charcot-Marie-Tooth (CMT) disease:
- the diagnosis of multiple cerebral malformations was made antenatally after the demonstration of lissencephaly, polymicrogyria and cerebellar atrophy,
- a whole genome genetic study (WGS) revealed a homozygous deletion of the MNF2 gene,
- functional studies, in vivo and in vitro (on fibroblasts) confirmed the pathogenicity of the variant by showing a disturbance in mitochondrial fusion and their accumulation in clusters in the cell.
These findings extend the phenotypic spectrum of mitofusinopathies, in which central nervous system involvement has already been reported but not to this level of severity.
