Human genetic disease caused by de novo mitochondrial-nuclear DNA transfer

Turner, C., Kiloran, C., Thomas, Nicholas Stuart, Rosenberg, M., Chuzhanova, N. A., Johnston, J., Kemel, Y., Cooper, David Neil ORCID: https://orcid.org/0000-0002-8943-8484 and Biesecker, L. G. 2003. Human genetic disease caused by de novo mitochondrial-nuclear DNA transfer. Human Genetics 112 (3) , pp. 303-309. 10.1007/s00439-002-0892-2

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Abstract

Transfer of nucleic acid from cytoplasmic organelles to the nuclear genome is a well-established mechanism of evolutionary change in eukaryotes. Such transfers have occurred throughout evolution, but so far, none has been shown unequivocally to occur de novo to cause a heritable human disease. We have characterized a patient with a de novo nucleic acid transfer from the mitochondrial to the nuclear genome, a transfer that is responsible for a sporadic case of Pallister-Hall syndrome, a condition usually inherited in an autosomal dominant fashion. This mutation, a 72-bp insertion into exon 14 of the GLI3 gene, creates a premature stop codon and predicts a truncated protein product. Both the mechanism and the cause of the mitochondrial-nuclear transfer are unknown. Although the conception of this patient was temporally and geographically associated with high-level radioactive contamination following the Chernobyl accident, this case cannot, on its own, be used to establish a causal relationship between radiation exposure and this rare type of mutation. Thus, for the time being, it must be considered as an intriguing coincidence. Nevertheless, these data serve to demonstrate that de novo mitochondrial-nuclear transfer of nucleic acid is a novel mechanism of human inherited disease.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General) R Medicine > RZ Other systems of medicine
Uncontrolled Keywords:	Substances DNA Complementary,DNA Mitochondrial,DNA-Binding Proteins,GLI3 protein Xenopus,GLI3 protein human,Gli3 protein mouse,Kruppel-Like Transcription Factors,Nerve Tissue Proteins,Repressor Proteins,Transcription Factors,Xenopus Proteins,DNA
Publisher:	Springer Verlag
ISSN:	0340-6717
Last Modified:	25 Oct 2022 10:04
URI:	https://orca.cardiff.ac.uk/id/eprint/61006

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