0000000000094678
AUTHOR
S. Efthymiou
Biallelic mutations in neurofascin cause neurodevelopmental impairment and peripheral demyelination
See Karakaya and Wirth (doi:10.1093/brain/awz273) for a scientific commentary on this article. Neurofascin (NFASC) isoforms are immunoglobulin cell adhesion molecules involved in node of Ranvier assembly. Efthymiou et al. identify biallelic NFASC variants in ten unrelated patients with a neurodevelopmental disorder characterized by variable degrees of central and peripheral involvement. Abnormal expression of Nfasc155 is accompanied by severe loss of myelinated fibres.
Age-dependent epileptic encephalopathy associated with an unusual co-occurrence of ZEB2 and SCN1A variants.
Mowat-Wilson syndrome is a genetic disorder associated with a variable phenotype including peculiar facial features associated with intellectual disability, epilepsy, language impairment, and multiple congenital anomalies caused by heterozygous mutation of the ZEB2 gene. The ZEB2 protein is a complex transcription factor that encompasses multiple functional domains that interact with the regulatory regions of target genes including those involved in brain development. Recently, it has been documented that ZEB2 regulates the differentiation of interneuron progenitors migrating from the medial ganglionic eminence to cortical layers by repression of the Nkx2-1 homeobox transcription factor. It…
Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants
Mice lacking GAD1 show neonatal mortality, but the human phenotype associated with GAD1 disruption is poorly characterized. Neuray et al. describe six patients with biallelic GAD1 mutations, presenting with early-infantile onset epilepsy, neurodevelopmental delay, muscle weakness and non-CNS manifestations.