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Exome sequencing id...
Exome sequencing identifies mitochondrial alanyl-tRNA synthetase mutations in infantile mitochondrial cardiomyopathy
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- Götz, Alexandra (författare)
- Research Programs Unit, Biomedicum-Helsinki, University of Helsinki, Helsinki, Finland
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- Tyynismaa, Henna (författare)
- Research Programs Unit, Biomedicum-Helsinki, University of Helsinki, Helsinki, Finland
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- Euro, Liliya (författare)
- Research Programs Unit, Biomedicum-Helsinki, University of Helsinki, Helsinki, Finland
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- Ellonen, Pekka (författare)
- Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
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- Hyötyläinen, Tuulia, 1971- (författare)
- VTT Technical Research Centre of Finland, Espoo, Finland
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- Ojala, Tiina (författare)
- Department of Pediatric Cardiology, Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
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- Hämäläinen, Riikka H (författare)
- Research Programs Unit, Biomedicum-Helsinki, University of Helsinki, Helsinki, Finland
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- Tommiska, Johanna (författare)
- Institute of Biomedicine, Department of Physiology, University of Helsinki, Helsinki, Finland; Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland g
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- Raivio, Taneli (författare)
- Institute of Biomedicine, Department of Physiology, University of Helsinki, Helsinki, Finland; Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland
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- Oresic, Matej, 1967- (författare)
- Örebro universitet,Institutionen för medicinska vetenskaper,VTT Technical Research Centre of Finland, Espoo, Finland
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- Karikoski, Riitta (författare)
- Department of Pathology, University of Helsinki, Helsinki, Finland; Helsinki University Central Hospital, Helsinki, Finland
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- Tammela, Outi (författare)
- Pediatric Research Centre, Tampere University Hospital, Tampere, Finland
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- Simola, Kalle O J (författare)
- Genetics Outpatient Clinic, Department of Pediatrics, Tampere University Hospital, Tampere, Finland
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- Paetau, Anders (författare)
- Department of Pathology, University of Helsinki, Helsinki, Finland; Helsinki University Central Hospital, Helsinki, Finland
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- Tyni, Tiina (författare)
- Research Programs Unit, Biomedicum-Helsinki, University of Helsinki, Helsinki, Finland; Department of Pediatric Neurology, Helsinki University Central Hospital, Helsinki, Finland
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- Suomalainen, Anu (författare)
- Research Programs Unit, Biomedicum-Helsinki, University of Helsinki, Helsinki, Finland; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland; Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland
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(creator_code:org_t)
- Cell Press, 2011
- 2011
- Engelska.
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Ingår i: American Journal of Human Genetics. - : Cell Press. - 0002-9297 .- 1537-6605. ; 88:5, s. 635-642
- Relaterad länk:
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http://www.cell.com/...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Infantile cardiomyopathies are devastating fatal disorders of the neonatal period or the first year of life. Mitochondrial dysfunction is a common cause of this group of diseases, but the underlying gene defects have been characterized in only a minority of cases, because tissue specificity of the manifestation hampers functional cloning and the heterogeneity of causative factors hinders collection of informative family materials. We sequenced the exome of a patient who died at the age of 10 months of hypertrophic mitochondrial cardiomyopathy with combined cardiac respiratory chain complex I and IV deficiency. Rigorous data analysis allowed us to identify a homozygous missense mutation in AARS2, which we showed to encode the mitochondrial alanyl-tRNA synthetase (mtAlaRS). Two siblings from another family, both of whom died perinatally of hypertrophic cardiomyopathy, had the same mutation, compound heterozygous with another missense mutation. Protein structure modeling of mtAlaRS suggested that one of the mutations affected a unique tRNA recognition site in the editing domain, leading to incorrect tRNA aminoacylation, whereas the second mutation severely disturbed the catalytic function, preventing tRNA aminoacylation. We show here that mutations in AARS2 cause perinatal or infantile cardiomyopathy with near-total combined mitochondrial respiratory chain deficiency in the heart. Our results indicate that exome sequencing is a powerful tool for identifying mutations in single patients and allows recognition of the genetic background in single-gene disorders of variable clinical manifestation and tissue-specific disease. Furthermore, we show that mitochondrial disorders extend to prenatal life and are an important cause of early infantile cardiac failure.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
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- art (ämneskategori)
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Götz, Alexandra
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Tyynismaa, Henna
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Euro, Liliya
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Ellonen, Pekka
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Hyötyläinen, Tuu ...
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Ojala, Tiina
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Hämäläinen, Riik ...
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Tommiska, Johann ...
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Raivio, Taneli
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Oresic, Matej, 1 ...
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Karikoski, Riitt ...
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Tammela, Outi
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Simola, Kalle O ...
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Paetau, Anders
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Tyni, Tiina
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Suomalainen, Anu
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Örebro universitet