A Novel Pathogenic Variant Identified in HIKESHI-Related Hypomyelinating Leukodystrophy Disrupts Heat Shock Response in iPSCs.

ABSTRACT: HIKESHI-related hypomyelinating leukodystrophy (HHL) is a life-threatening disorder caused by homozygous pathogenic variants in HIKESHI. Symptoms include infantile onset progressive spastic dystonic quadriplegia, nystagmus, failure to thrive, diffused hypomyelination, and severe morbidity or death following febrile illness. V54L variants in HIKESHI are particularly prevalent within the Ashkenazi Jewish population. Here, we identified a novel P78S disease-causing variant in HIKESHI in a patient of Christian Arab origin, presenting with clinical and radiologic features characteristic of HHL. In silico analysis suggests that the mutated residue may affect the HIKESHI protein's dimerization domain. We generated a comprehensive set of induced pluripotent stem cells (iPSCs)

SUBMITTER: Saleh MA 

PROVIDER: S-EPMC12250047 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature