| Autor: |
D, Verrigni, D, Diodato, M, Di Nottia, A, Torraco, E, Bellacchio, T, Rizza, G, Tozzi, M, Verardo, F, Piemonte, G, Tasca, A, D'Amico, E, Bertini, R, Carrozzo |
| Rok vydání: |
2016 |
| Předmět: |
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| Zdroj: |
Clinical genetics. 91(6) |
| ISSN: |
1399-0004 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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