The mutant rats did not show reactive gliosis by then but exhibited hypomyelination and increased extracellular fluid in the corpus callosum.CONCLUSIONSThe CRISPR/Cas9-mediated genome editing system can be harnessed to efficiently disrupt the L1cam gene in rats for creation of a larger XLH animal model than previously available.
The great proportion of XLH is ascribed to loss-of-function mutations of L1 cell adhesion molecule gene (<i>L1CAM</i>), but silent mutations in <i>L1CAM</i> with pathogenic potential were rare and were usually ignored especially in whole-exome sequencing (WES) detection.
L1CAM molecule is a cell adhesion molecule in nervous and enteric systems and is responsible for X-linked hydrocephalus (XLH) spectrum, which is a rare condition with severe congenital hydrocephalus, dysgenesis of the corpus callosum, intellectual disability, spasticity, and adducted thumbs.
While it is obvious that additional studies are necessary to further delineate the association between XLH and HSCR in the presence of L1CAM mutations, the documentation of this new patient reinforces the role of this gene acting either in a direct or indirect way in the pathogenesis of Hirschsprung disease.
The association of HSCR with XLH in the presence of L1CAM mutations remains quite interesting because cell adhesion molecules are involved in the proper migration of neural components throughout the body.
Herein, we report 2 cases--the first showed abnormality of the L1CAM genes and developed HSCR; and the second, with clinically suspected XLH, was successfully operated on for HSCR.