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The genotypic and phenotypic spectrum of MTO1 deficiency
Molecular Genetics and Metabolism, 123 (2018), 1; 28-42. https://doi.org/doi:10.1016/j.ymgme.2017.11.003
O'Byrne, James J.; Tarailo-Graovac, Maja; Ghani, Aisha; Champion, Michael; Deshpande, Charu; Dursun, Ali; Ozgul, Riza K.; Freisinger, Peter; Garber, Ian; Haack, Tobias B.; Horvath, Rita; Barić, Ivo; Husain, Ralf A.; Kluijtmans, Leo A.J.; Kotzaeridou, Urania; Morris, Andrew A.; Ross, Colin J.; Santra, Saikat; Smeitink, Jan; Tarnopolsky, Mark; Wortmann, Saskia B.; Mayr, Johannes A.; Brunner-Krainz, Michaela; Prokisch, Holger; Wasserman, Wyeth W.; Wevers, Ron A.; Engelke, Udo F.; Rodenburg, Richard J.; Ting, Teck Wah; McFarland, Robert; Taylor, Robert W.; Salvarinova, Ramona; van Karnebeek, Clara D.M. Više autora...

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O'Byrne, J. J., Tarailo Graovac, M., Ghani, A., Champion, M., Deshpande, C., Dursun, A. ... van Karnebeek, C. D. (2018). The genotypic and phenotypic spectrum of MTO1 deficiency. Molecular Genetics and Metabolism, 123. (1), 28-42. doi: doi:10.1016/j.ymgme.2017.11.003

O'Byrne, James J., et al. "The genotypic and phenotypic spectrum of MTO1 deficiency." Molecular Genetics and Metabolism, vol. 123, br. 1, 2018, str. 28-42. https://doi.org/doi:10.1016/j.ymgme.2017.11.003

O'Byrne, James J., Maja Tarailo Graovac, Aisha Ghani, Michael Champion, Charu Deshpande, Ali Dursun, Riza K. Ozgul, et al. "The genotypic and phenotypic spectrum of MTO1 deficiency." Molecular Genetics and Metabolism 123, br. 1 (2018): 28-42. https://doi.org/doi:10.1016/j.ymgme.2017.11.003

O'Byrne, J. J., et al. (2018) 'The genotypic and phenotypic spectrum of MTO1 deficiency', Molecular Genetics and Metabolism, 123(1), str. 28-42. doi: doi:10.1016/j.ymgme.2017.11.003

O'Byrne JJ, Tarailo Graovac M, Ghani A, Champion M, Deshpande C, Dursun A, i sur.. The genotypic and phenotypic spectrum of MTO1 deficiency. Molecular Genetics and Metabolism [Internet]. 01.2018. [pristupljeno 13.07.2024.];123(1):28-42. doi: doi:10.1016/j.ymgme.2017.11.003

J. J. O'Byrne, et al., "The genotypic and phenotypic spectrum of MTO1 deficiency", Molecular Genetics and Metabolism, vol. 123, br. 1, str. 28-42, Siječanj 2018. [Online]. Dostupno na: https://urn.nsk.hr/urn:nbn:hr:105:174440. [Citirano: 13.07.2024.]

Za citiranje koristite ovu mrežnu adresu: https://urn.nsk.hr/urn:nbn:hr:105:174440
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Naslov (engleski)The genotypic and phenotypic spectrum of MTO1 deficiency
AutorJames J. O'Byrne
AutorMaja Tarailo-Graovac
AutorAisha Ghani
AutorMichael Champion
AutorCharu Deshpande
AutorAli Dursun
AutorRiza K. Ozgul
AutorPeter Freisinger
AutorIan Garber
AutorTobias B. Haack
AutorRita Horvath
AutorIvo Barić
AutorRalf A. Husain
AutorLeo A.J. Kluijtmans
AutorUrania Kotzaeridou
AutorAndrew A. Morris
AutorColin J. Ross
AutorSaikat Santra
AutorJan Smeitink
AutorMark Tarnopolsky
AutorSaskia B. Wortmann
AutorJohannes A. Mayr
AutorMichaela Brunner-Krainz
AutorHolger Prokisch
AutorWyeth W. Wasserman
AutorRon A. Wevers
AutorUdo F. Engelke
AutorRichard J. Rodenburg
AutorTeck Wah Ting
AutorRobert McFarland
AutorRobert W. Taylor
AutorRamona Salvarinova
AutorClara D.M. van Karnebeek
Autorova ustanovaSveučilište u Zagrebu
Medicinski fakultet
Znanstveno / umjetničko
područje, polje i grana		BIOMEDICINA I ZDRAVSTVO
Temeljne medicinske znanosti
Sažetak (engleski)
BACKGROUND: Mitochondrial diseases, a group of multi-systemic disorders often characterized by tissue-specific phenotypes, are usually progressive and fatal disorders resulting from defects in oxidative phosphorylation. MTO1 (Mitochondrial tRNA Translation Optimization 1), an evolutionarily conserved protein expressed in high-energy demand tissues has been linked to human early-onset combined oxidative phosphorylation deficiency associated with hypertrophic cardiomyopathy, often referred to as combined oxidative phosphorylation deficiency-10 (COXPD10). ----- MATERIAL AND METHODS: Thirty five cases of MTO1 deficiency were identified and reviewed through international collaboration. The cases of two female siblings, who presented at 1 and 2years of life with seizures, global developmental delay, hypotonia, elevated lactate and complex I and IV deficiency on muscle biopsy but without cardiomyopathy, are presented in detail. ----- RESULTS: For the description of phenotypic features, the denominator varies as the literature was insufficient to allow for complete ascertainment of all data for the 35 cases. An extensive review of all known MTO1 deficiency cases revealed the most common features at presentation to be lactic acidosis (LA) (21/34; 62% cases) and hypertrophic cardiomyopathy (15/34; 44% cases). Eventually lactic acidosis and hypertrophic cardiomyopathy are described in 35/35 (100%) and 27/34 (79%) of patients with MTO1 deficiency, respectively; with global developmental delay/intellectual disability present in 28/29 (97%), feeding difficulties in 17/35 (49%), failure to thrive in 12/35 (34%), seizures in 12/35 (34%), optic atrophy in 11/21 (52%) and ataxia in 7/34 (21%). There are 19 different pathogenic MTO1 variants identified in these 35 cases: one splice-site, 3 frameshift and 15 missense variants. None have bi-allelic variants that completely inactivate MTO1; however, patients where one variant is truncating (i.e. frameshift) while the second one is a missense appear to have a more severe, even fatal, phenotype. These data suggest that complete loss of MTO1 is not viable. A ketogenic diet may have exerted a favourable effect on seizures in 2/5 patients. ----- CONCLUSION: MTO1 deficiency is lethal in some but not all cases, and a genotype-phenotype relation is suggested. Aside from lactic acidosis and cardiomyopathy, developmental delay and other phenotypic features affecting multiple organ systems are often present in these patients, suggesting a broader spectrum than hitherto reported. The diagnosis should be suspected on clinical features and the presence of markers of mitochondrial dysfunction in body fluids, especially low residual complex I, III and IV activity in muscle. Molecular confirmation is required and targeted genomic testing may be the most efficient approach. Although subjective clinical improvement was observed in a small number of patients on therapies such as ketogenic diet and dichloroacetate, no evidence-based effective therapy exists.
Ključne riječi (engleski)
Jezikengleski
Vrsta publikacijeZnanstveni rad - Izvorni znanstveni rad
Status objaveObjavljen
Vrsta recenzijeRecenziran
Verzija publikacijeObjavljena verzija rada (izdavačev PDF)
Naslov časopisaMolecular Genetics and Metabolism
Brojčani podacivol. 123, br. 1, str. 28-42
p-ISSN1096-7192
DOIhttps://doi.org/doi:10.1016/j.ymgme.2017.11.003
URN:NBNurn:nbn:hr:105:174440
Datum objave publikacije2018-01
URL dokumentahttp://doi.org/10.1016/j.ymgme.2017.11.003
Vrsta resursaTekst
Prava pristupaOtvoreni pristup
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Datum i vrijeme pohrane2024-03-28 10:12:38