Generation of three induced pluripotent stem cell lines from individuals with late infantile TUBB4A-associated leukodystrophy caused by a c.1172G > A (p.R391H) de novo mutation in TUBB4A.

A de novo variant, c.1172G > A (p. Arg391His) inTUBB4A causes late infantile TUBB4A-associated leukodystrophy with MRI features of isolated hypomyelination. To model and understand the disease pathology, we generated three induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells of affected individuals using Sendai viral-mediated reprogramming under feeder-free conditions. All lines displayed normal morphology, expressed undifferentiated iPSC state markers, demonstrated trilineage differentiation, and showed normal STR identity, karyotype, and absence of reprogramming vectors. The reprogrammed iPSCs will enable us to model the isolated hypomyelination phenotype, dissect the underlying cellular mechanisms, and test various treatment targets.