Novel case of neurodegeneration with brain iron accumulation 4 (NBIA4) caused by a pathogenic variant affecting splicing

Abstract

Neurodegeneration with brain iron accumulation type 4 (NBIA4) also known as MPAN (mitochondria protein-associated neurodegeneration) is a rare neurological disorder which main feature is brain iron accumulation most frequently in the globus pallidus and substantia nigra. Whole exome sequencing (WES) in a 12-year-old patient revealed 2 variants in the C19orf12 gene, a previously reported common 11 bp deletion c.204_214del11, p.(Gly69Argfs*10) and a novel splicing variant c.193+5G>A. Functional analysis of novel variant showed skipping of the second exon, resulting in a formation of a truncated nonfunctional protein. This is the first functionally annotated pathogenic splicing variant in NBIA4.

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Correspondence to Peter Sparber.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Sparber, P., Marakhonov, A., Filatova, A. et al. Novel case of neurodegeneration with brain iron accumulation 4 (NBIA4) caused by a pathogenic variant affecting splicing. Neurogenetics 19, 257–260 (2018). https://doi.org/10.1007/s10048-018-0558-4

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Keywords

  • MPAN
  • NBIA
  • C19orf12
  • Neurodegeneration
  • Iron accumulation
  • Functional analysis
  • Splicing