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Subcortical laminar heterotopia (SCLH) is a neuronal migration disorder in which a band of heterotopic gray matter runs parallel to the normal cerebral cortex separated by a thin layer of white matter. Many patients with SCLH are female, and about a half of them are heterozygotes for a loss-of-function mutation in the DCX (XLIS) gene encoded in chromosome Xq22.3-q23.1-3⇓⇓ Rare male cases may be caused by a mutation in either the DCX or LIS1 gene, the latter being encoded in chromosome 17p13.3.4 In the remaining patients, the causative mutation is unknown.
Expression of the DCX gene product, doublecortin, is high in the fetal CNS neurons but declines postnatally.5 Although it is presumed that doublecortin is reduced in the brain of many SCLH patients, pathologic evidence for this is scarce because it is extremely difficult to obtain brain tissues of this rare, nonfatal anomaly in the fetal period when physiologic expression of doublecortin is robust.
We recently had an opportunity to examine the brain of …
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