Transfer of a mitochondrial DNA fragment to MCOLN1 causes an inherited case of mucolipidosis IV

Hum Mutat. 2004 Dec;24(6):460-5. doi: 10.1002/humu.20094.


A patient with mucolipidosis-IV heterozygous for two mutations in MCOLN1 expressed only her father's cDNA mutation c.1207C>T predicting an R403C change in mucolipin. She inherited a 93bp segment from mitochondrial NADH dehydrogenase 5 (MTND5) from her mother that was inserted in-frame prior to the last nucleotide of exon 2 of MCOLN1 (c.236_237ins93). This alteration abolished proper splicing of MCOLN1. The splice site at the end of the exon was not used due to an inhibitory effect of the inserted segment, resulting in two aberrant splice products containing stop codons in the downstream intron. These products were eliminated via nonsense-mediated decay. This is the first report of an inherited transfer of mitochondrial nuclear DNA causing a genetic disease. The elimination of the splice site by the mitochondrial DNA requires a change in splicing prediction models.

Publication types

  • Case Reports

MeSH terms

  • Base Sequence
  • Child, Preschool
  • DNA Mutational Analysis
  • DNA, Complementary
  • DNA, Mitochondrial*
  • Female
  • Humans
  • Membrane Proteins / genetics*
  • Models, Genetic
  • Molecular Sequence Data
  • Mucolipidoses / genetics*
  • Mutagenesis, Insertional
  • Mutation, Missense
  • RNA Splicing / genetics
  • TRPM Cation Channels
  • Transient Receptor Potential Channels


  • DNA, Complementary
  • DNA, Mitochondrial
  • MCOLN1 protein, human
  • Membrane Proteins
  • TRPM Cation Channels
  • Transient Receptor Potential Channels

Associated data

  • OMIM/25650
  • OMIM/516005
  • OMIM/605248