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EnglishThiamine 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.
| Titolo: | Functional analysis of the third identified SLC25A19 mutation causative for the thiamine metabolism dysfunction syndrome 4 |
| Autori: | |
| Data di pubblicazione: | 2019 |
| Stato di pubblicazione: | Pubblicato |
| Rivista: | |
| Abstract: | 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. |
| Handle: | http://hdl.handle.net/11368/2958867 |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1038/s10038-019-0666-5 |
| URL: | https://www.nature.com/articles/s10038-019-0666-5#Sec17 |
| Appare nelle tipologie: | 1.1 Articolo in Rivista |
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| bottega2019.pdf | Versione finale del lavoro | Documento in Versione Editoriale | Copyright Editore | Administrator Richiedi una copia |
| 10038_2019_666_MOESM1_ESM.pdf | Supplementary material | Documento in Versione Editoriale | Copyright Editore | Administrator Richiedi una copia |
