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

The SOX1O transcription factor is involved in development of neural crest d erivatives and fate determination in glial cells. SOX10 mutations have been found in patients with intestinal aganglionosis and depigmentation with de afness (Waardenburg-Hirschsprung). Associated neurological signs have been reported in some cases, including a patient exhibiting a central and periph eral myelin deficiency. Therefore, we screened for SOX10 mutations in a lar ge cohort of patients with peripheral and central myelin disorders. 56 were affected by classical demyelinating Charcot-Marie-Tooth disease without id entified mutations in the genes encoding PNS myelin proteins (PMP22, PO), c onnexin 32 and the zinc-finger transcription factor, EGR2. 88 patients with undetermined leukodystrophy were selected from a large European prospectiv e study. Associated clinical, magnetic resonance imaging and electrophysiol ogical signs were consistent with a defect in CNS myelination in 83 and wit h an active degeneration of the CNS myelin in 5. No abnormalities in the pr oteolipid protein gene (PLP) were found. The absence of SOX10 mutation in t his large cohort of patients suggests that this gene is not frequently invo lved in peripheral or central inherited myelin disorders.