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Infantile onset encephalomyopathy,retinopathy, optic atrophy,and mitochondrial DNA depletion associated with a novel pathogenic DHX16 variant |
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| Authors: | Milla-Riikka Hautakangas Paula Widgren Paavo Korpelainen Salla M Kangas Tuomas Komulainen Päivi Vieira Elisa Rahikkala Katri Pylkäs Hannu Tuominen Hannaleena Kokkonen Ilkka Miinalainen Javad Nadaf Jacek Majewski Reetta Hinttala Johanna Uusimaa |
| Institution: | 1. Research Unit of Clinical Medicine, Medical Research Center, University of Oulu, Oulu, Finland;2. Research Unit of Clinical Medicine, Medical Research Center, University of Oulu, Oulu, Finland
Oulu University Hospital, Oulu, Finland;3. Biocenter Oulu, University of Oulu, Oulu, Finland;4. Oulu University Hospital, Oulu, Finland;5. Research Unit of Clinical Medicine, Medical Research Center, University of Oulu, Oulu, Finland Northern Finland Laboratory Centre Oulu, Oulu, Finland;6. Department of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill University, Montreal, Quebec, Canada;7. Department of Human Genetics, McGill University, Montreal, Quebec, Canada;8. Research Unit of Clinical Medicine, Medical Research Center, University of Oulu, Oulu, Finland Biocenter Oulu, University of Oulu, Oulu, Finland |
| Abstract: | We studied a patient with mitochondrial DNA depletion in skeletal muscle and a multiorgan phenotype, including fatal encephalomyopathy, retinopathy, optic atrophy, and sensorineural hearing loss. Instead of pathogenic variants in the mitochondrial maintenance genes, we identified previously unpublished variant in DHX16 gene, a de novo heterozygous c.1360C>T (p. Arg454Trp). Variants in DHX16 encoding for DEAH-box RNA helicase have previously been reported only in five patients with a phenotype called as neuromuscular oculoauditory syndrome including developmental delay, neuromuscular symptoms, and ocular or auditory defects with or without seizures. We performed functional studies on patient-derived fibroblasts and skeletal muscle revealing, that the DHX16 expression was decreased. Clinical features together with functional data suggest, that our patient's disease is associated with a novel pathogenic DHX16 variant, and mtDNA depletion could be a secondary manifestation of the disease. |
| Keywords: | DHX16 encephalomyopathy mitochondrial DNA depletion optic atrophy retinopathy |