Candidate CSPG4 mutations and induced pluripotent stem cell modeling implicate oligodendrocyte progenitor cell dysfunction in familial schizophrenia.

ABSTRACT: Schizophrenia is highly heritable, yet its underlying pathophysiology remains largely unknown. Among the most well-replicated findings in neurobiological studies of schizophrenia are deficits in myelination and white matter integrity; however, direct etiological genetic and cellular evidence has thus far been lacking. Here, we implement a family-based approach for genetic discovery in schizophrenia combined with functional analysis using induced pluripotent stem cells (iPSCs). We observed familial segregation of two rare missense mutations in Chondroitin Sulfate Proteoglycan 4 (CSPG4) (c.391G > A [p.A131T], MAF 7.79 × 10^-5 and c.2702T > G [p.V901G], MAF 2.51 × 10^-3). The CSPG4^A131T mutation was absent from the Swedish Schizophrenia Exome Sequencing Study (2

SUBMITTER: de Vrij FM 

PROVIDER: S-EPMC6755981 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature