Concatenated mitochondrial segments in human genetic disorders: a case study

The transfer of nucleic acid from mitochondria to the nuclear genome produces nuclear–mitochondrial segments (NUMTs). Here, we identified a patient carrying a 34.8-kb duplication in DMD intron 1, with a 57.7-kb NUMT insertion located between these duplicated regions. Nanopore ultra-long sequencing revealed that this NUMT comprises eight concatenated mitochondrial fragments. Analysis of RNA validation revealed allele-specific expression of the DMD gene in the mother’s muscle tissue, highlighting the lack of transcription of the mutated DMD allele. To our knowledge, this case is the first documented instance of a genetic disorder resulting from the insertion of a concatenated NUMT.