1. Functional analysis of the third identified SLC25A19 mutation causative for the thiamine metabolism dysfunction syndrome 4
- Author
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Bottega, Roberta, Perrone, Maria D, Vecchiato, Katy, Taddio, Andrea, Sabui, Subrata, Pecile, Vanna, Said, Hamid M, and Faletra, Flavio
- Subjects
Biological Sciences ,Bioinformatics and Computational Biology ,Biomedical and Clinical Sciences ,Nutrition ,Neurodegenerative ,Brain Disorders ,Genetics ,Rare Diseases ,Neurosciences ,Peripheral Neuropathy ,Clinical Research ,2.1 Biological and endogenous factors ,Aetiology ,Good Health and Well Being ,Adolescent ,Brain Diseases ,Genetic Predisposition to Disease ,Humans ,Male ,Microcephaly ,Mitochondrial Membrane Transport Proteins ,Mutation ,Protein Conformation ,RNA ,Messenger ,Thiamine ,Thiamine Deficiency ,Clinical Sciences ,Genetics & Heredity ,Clinical sciences - 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.
- Published
- 2019