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- Title
Novel mutations in KARS cause hypertrophic cardiomyopathy and combined mitochondrial respiratory chain defect.
- Authors
Verrigni, D.; Diodato, D.; Di Nottia, M.; Torraco, A.; Bellacchio, E.; Rizza, T.; Tozzi, G.; Verardo, M.; Piemonte, F.; Tasca, G.; D'Amico, A.; Bertini, E.; Carrozzo, R.
- Abstract
Mutations in KARS, which encodes for both mitochondrial and cytoplasmic lysyl- tRNA synthetase, have been so far associated with three different phenotypes: the recessive form of Charcot-Mary-Tooth polyneuropathy, the autosomal recessive nonsyndromic hearing loss and the last recently described condition related to congenital visual impairment and progressive microcephaly. Here we report the case of a 14-year-old girl with severe cardiomyopathy associated to mild psychomotor delay and mild myopathy; moreover, a diffuse reduction of cytochrome C oxidase ( COX, complex IV) and a combined enzymatic defect of complex I ( CI) and complex IV ( CIV) was evident in muscle biopsy. Using the TruSight One sequencing panel we identified two novel mutations in KARS. Both mutations, never reported previously, occur in a highly conserved region of the catalytic domain and displayed a dramatic effect on KARS stability. Structural analysis confirmed the pathogenic role of the identified variants. Our findings confirm and emphasize that mt-aminoacyl-tRNA synthetases (mt- ARSs) enzymes are related to a broad clinical spectrum due to their multiple and still unknown functions.
- Subjects
GENETIC mutation; HYPERTROPHIC cardiomyopathy; MITOCHONDRIA; TRANSFER RNA; VISION disorders
- Publication
Clinical Genetics, 2017, Vol 91, Issue 6, p918
- ISSN
0009-9163
- Publication type
Article
- DOI
10.1111/cge.12931