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.

中文翻译：

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由影响剪接的致病性变异引起的脑退行性神经蓄积4（NBIA4）引起的神经退行性新病例。

具有脑铁蓄积类型4（NBIA4）的神经变性也称为MPAN（线粒体蛋白相关的神经变性）是一种罕见的神经系统疾病，主要特征是苍白球和黑质中脑铁蓄积最多。一名12岁患者的全外显子组测序（WES）显示C19orf12基因有2个变异，先前报道的常见11 bp缺失c.204_214del11，p。（Gly69Argfs * 10）和新的剪接变异c.193 + 5G > A。新变体的功能分析显示第二个外显子被跳过，导致截短的非功能蛋白的形成。这是NBIA4中第一个功能注释的病原体剪接变体。