Stroke-Like Lesions Can Be a Manifestation of Variants in Ndna Located Mitochondrial Genes

We read with interest the article by Xie et al. about a 51yo female with nuclear inclusion disease (NID) due to a GGC expansion of 118 repeats in NOTCH2NLC detected upon a repeat-primed PCR [1]. The patient manifested phenotypically with migraine, lactic acidosis, and a stroke-like lesion (SLL) in the right occipito-temporal area at age 51y [1]. A mitochondrial disorder (MID) was considered as a differential but excluded upon sequencing of the mitochondrial DNA (mtDNA) and application of a gene panel for mutations in nuclear DNA (nDNA) located genes involved in mitochondrial function and morphology [1]. It was concluded that a NID should be considered as a differential of migraine and a SLL and that hyperintensity on diffusion weighted imaging (DWI) and cortical enhancement could be a biomarker of NID [1]. The study is appealing but raises concerns which should be extensively discussed