Functional analysis of the third identified SLC25A19 mutation causative for the thiamine metabolism dysfunction syndrome 4

Roberta Bottega, Maria D. Perrone, Katy Vecchiato, Andrea Taddio, Subrata Sabui, Vanna Pecile, Hamid M. Said, Flavio Faletra

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Thiamine metabolism dysfunction syndrome-4 (THMD4) includes episodic encephalopathy, often associated with a febrile illness, causing transient neurologic dysfunction and a slowly progressive axonal polyneuropathy. Until now only two mutations (G125S and S194P) have been reported in the SLC25A19 gene as causative for this disease and a third mutation (G177A) as related to the Amish lethal microcephaly. In this work, we describe the clinical and molecular features of a patient carrying a novel mutation (c.576G>C; Q192H) on SLC25A19 gene. Functional studies on this mutation were performed explaining the pathogenetic role of c.576G>C in affecting the translational efficiency and/or stability of hMTPPT protein instead of the mRNA expression. These findings support the pathogenetic role of Q192H (c.576G>C) mutation on SLC25A19 gene. Moreover, despite in other patients the thiamine supplementation leaded to a substantial improvement of peripheral neuropathy, our patient did not show a clinical improvement.

Original languageEnglish
Pages (from-to)1075-1081
Number of pages7
JournalJournal of Human Genetics
Issue number11
Publication statusPublished - Nov 1 2019


ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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