LBSL: Case Series and DARS2 Variant Analysis in Early Severe Forms With Unexpected Presentations.
Menno D StellingwerffSonia FigucciaEmanuele BellacchioKarin AlvarezClaudia CastiglioniPinar TopalogluChloe A StutterdCorrie E ErasmusAmarilis Sanchez-ValleSebastien LebonSarah HughesThomas Schmitt-MechelkeGessica VascoGabriel ChowElisa RahikkalaCristina DallabonaCecilia OkumaChiara AielloPaola GoffriniTruus E M AbbinkEnrico S BertiniMarjo S Van der KnaapPublished in: Neurology. Genetics (2021)
DARS2 variants are associated with highly heterogeneous phenotypes. New MRI presentations are profound cerebral hypoplasia/atrophy and white matter abnormalities without long tract involvement. Our findings have implications for diagnosis and understanding disease mechanisms, pointing at dominant neuronal/axonal involvement in severe cases. In line with this conclusion, activation of biallelic DARS2 null alleles in conditional transgenic mice leads to massive neuronal apoptosis.
Keyphrases
- white matter
- intellectual disability
- cerebral ischemia
- early onset
- magnetic resonance imaging
- subarachnoid hemorrhage
- spinal cord injury
- endoplasmic reticulum stress
- contrast enhanced
- cell death
- copy number
- multiple sclerosis
- drug induced
- diffusion weighted imaging
- computed tomography
- cell proliferation
- blood brain barrier
- signaling pathway
- autism spectrum disorder