Altered PLP1 splicing causes hypomyelination of early myelinating structures.

ABSTRACT:

Objective

The objective of this study was to investigate the genetic etiology of the X-linked disorder "Hypomyelination of Early Myelinating Structures" (HEMS).

Methods

We included 16 patients from 10 families diagnosed with HEMS by brain MRI criteria. Exome sequencing was used to search for causal mutations. In silico analysis of effects of the mutations on splicing and RNA folding was performed. In vitro gene splicing was examined in RNA from patients' fibroblasts and an immortalized immature oligodendrocyte cell line after transfection with mutant minigene splicing constructs.

Results

All patients had unusual hemizygous mutations of PLP1 located in exon 3B (one deletion, one missense and two silent), which is spliced out in isoform DM20, or in intron 3 (five mutati

SUBMITTER: Kevelam SH 

PROVIDER: S-EPMC4479525 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature