Mitochondrial DNA depletion syndrome (MNGIE)
Definition
Biallelic pathogenic variants in the TYMP gene cause a deficiency of thymidine phosphorylase; the resulting enzyme deficiency leads to systemic accumulation of thymidine/deoxyuridine, which disrupts the mitochondrial deoxynucleotide pool and causes mitochondrial DNA deletions/depletion. The clinical picture typically begins in adolescence or early adulthood with severe gastrointestinal dysmotility, cachexia, ptosis, and peripheral neuropathy.
Gene/region analyzed
TYMP - Exon 2, TYMP - Exon 3, TYMP - Exon 4, TYMP - Exon 5, TYMP - Exon 6, TYMP - Exon 7, TYMP - Exon 8, TYMP - Exon 9, TYMP - Exon 10
Method
Sequence analysis
Accepted sample types
EDTA blood, AF, CVS
Inheritance
Hereditary, autosomal recessive.