The SOX10 transcription factor: evaluation as a candidate gene for central and peripheral hereditary myelin disorders

The SOX10transcription factor is involved in development of neural crestderivatives and fate determination in glial cells. SOX10mutations have been found in patients with intestinal aganglionosis and depigmentationwith deafness (Waardenburg-Hirschsprung). Associated neurological signs have been reported in some cases, including a patient exhibiting a central and peripheral myelindeficiency. Therefore, we screened for SOX10mutations in a large cohort of patients with peripheral and central myelindisorders. 56 were affected by classical demyelinating Charcot-Marie- Tooth diseasewithout identified mutations in the genes encoding PNS myelinproteins (PMP22, P0), connexin 32and the zinc-finger transcription factor, EGR2. 88 patients with undetermined leukodystrophywere selected from a large European prospective study. Associated clinical, magnetic resonance imaging and electrophysiological signs were consistent with a defect in CNS myelinationin 83 and with an active degeneration of the CNS myelinin 5. No abnormalities in the proteolipidprotein gene (PLP) were found. The absence of SOX10mutation in this large cohort of patients suggests that this gene is not frequently involved in peripheral or central inherited myelindisorders.