# name
A novel hypomorphic splice variant in EIF2B5 gene is associated with mild ovarioleukodystrophy

# metadata.dc.description.abstract[].value
Objective: To identify the genetic cause in an adult ovarioleukodystrophy patient resistant to diagnosis. Methods: We applied whole-exome sequencing (WES) to a vanishing white matter disease patient associated with premature ovarian failure at 26 years of age. We functionally tested an intronic variant by RT-PCR on patient's peripheral blood mononuclear cells (PBMC) and by minigene splicing assay. Results: WES analysis identified two novel variants in the EIF2B5 gene: c.725A > G (p.Tyr242Cys) and an intronic noncanonical mutation (c.1156 + 13G>A). This intronic mutation resulted into generation of various isoforms both in patient's PBMC and in the minigene splicing assay, showing that ~20% residual wild-type isoform is still expressed by the intronic-mutated allele alone, concordant with an hypomorphic effect of this variant. Conclusion: We report two novel variants in EIF2B5, one of them a noncanonical intronic splice variant, located at a +13 intronic position. This position is mutated only in 0.05% of ClinVar intronic mutations described so far. Furthermore, we illustrate how minigene splicing assay may be advantageous when validating splice-altering variants, in this case highlighting the coexistence of wild-type and mutated forms, probably explaining this patient's milder, late-onset phenotype.

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Annals of Clinical and Translational Neurology, 2020, vol. 7, num. 9, p. 1574-1579

# metadata.dc.rights[].value
cc by (c) Rodríguez Palmero et al., 2020

# metadata.dc.source[].value
Articles publicats en revistes (Ciències Clíniques)

# metadata.dc.title[].value
A novel hypomorphic splice variant in EIF2B5 gene is associated with mild ovarioleukodystrophy