The homozygous R504C mutation in MTO1 gene is responsible for ONCE syndrome |
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| Authors: | G. Barcia A. Delmiro M.E. Rodríguez‐García A. Blázquez R. Francisco‐Álvarez E. Martín‐Hernández P. Quijada‐Fraile P. Tejada‐Palacios J. Arenas C. Santos F. Martínez‐Azorín |
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| Affiliation: | 1. Department of Genetics, H?pital Necker‐Enfants‐Malades, Paris, France;2. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain;3. Laboratorio de Enfermedades Mitocondriales, Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain;4. Universidad Francisco de Vitoria, Facultad de Ciencias Experimentales, Madrid, Spain;5. Unidad de Enfermedades Metabólicas Hereditarias, Hospital 12 de Octubre, Madrid, Spain;6. Facultad de Medicina, Universidad Complutense de Madrid (UCM), Madrid, Spain;7. Departamento de Oftalmología, Hospital 12 de Octubre, Madrid, Spain |
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| Abstract: | We report clinical and biochemical finding from three unrelated patients presenting ONCE (Optic Neuropathy, Cardiomyopathy and Encephalopathy with lactic acidosis and combined oxidative phosphorylation deficiency) syndrome. Whole‐exome sequencing (WES) of the three patients and the healthy sister of one of them was used to identify the carry gene. Clinical and biochemical findings were used to filter variants, and molecular, in silico and genetic studies were performed to characterize the candidate variants. Mitochondrial DNA (mtDNA) defects involving mutations, deletions or depletion were discarded, whereas WES uncovered a double homozygous mutation in the MTO1 gene (NM_001123226:c.1510C>T, p.R504C, and c.1669G>A, p.V557M) in two of the patients and the homozygous mutation p.R504C in the other. Therefore, our data confirm p.R504C as pathogenic mutation responsible of ONCE syndrome, and p.V557M as a rare polymorphic variant. |
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| Keywords: | encephalopathy hypertrophic cardiomyopathy mitochondria mtDNA MTO1 optic atrophy WES |
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