Bi-allelic variants in FSD1L cause a neurodevelopmental disorder overlapping with L1 syndrome - PubMed
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- #L1 syndrome
- #neurodevelopmental disorder
- #FSD1L
- Bi-allelic variants in FSD1L cause a neurodevelopmental disorder overlapping with L1 syndrome.
- Eleven individuals, including five fetuses from six unrelated families, were identified with pathogenic variants in FSD1L.
- The disorder ranges from severe hydrocephalus and corpus callosum agenesis to severe intellectual disability, spastic tetraparesis, and epilepsy.
- The phenotype resembles L1 syndrome, caused by variants in L1CAM.
- Mouse embryo knockdown of Fsd1l recapitulated ventricular dilation seen in affected fetuses.
- FSD1L localizes to neurons with commissural fate and projection neurons during human development.
- iPSC-derived neural progenitor cells from affected individuals failed to differentiate properly and showed increased cell death.
- FSD1L interacts with microtubules during mitosis and the primary cilium during interphase.
- Fibroblasts from affected individuals showed altered mitotic spindle and reduced ciliogenesis.
- FSD1L is implicated in neuronal differentiation, axon guidance, and fasciculation.