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A homozygous mutation in IBA57 involved in intramitochondrial iron-sulfur cluster synthesis causes severe encephalopathy and mypathy in two neonates

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Abstract
Background: Combined OXPHOS deficiencies involving complexes I and II have recently been detected in patients with deficient iron-sulfur cluster (ISC) biogenesis. So far, patients were reported with pathogenic mutations in NFU1 and BOLA3 presenting with severe encephalomyopathy at young age. Objective: Two siblings with combined deficiency of complex I and II were investigated for possible defect in ISC. Patients and methods: The siblings presented soon after birth with severe encephalomyopathy and died in the neonatal period. Biochemical investigations showed increased lactate in serum and increased glycine in CSF. Considering the consanguineous descent a search for genes in homozygous regions related to ISC metabolism was performed. Results: Isolating IBA57 as a strong candidate gene, sequencing detected a homozygous mutation (c.941A>C) in the two siblings and a heterozygous carrier status in both parents. Western blotting showed a severe decrease of CRM for the IBA57 protein. The protein amount in the complexes I and II was significantly decreased. Transfection experiments in HeLa cells demonstrated that the mutation was pathogenic and that excessive degradation of the IBA57 protein was responsible for the defective ISC biosynthesis. Conclusion: This is the first report of a pathogenic mutation in IBA57 in human.
Keywords
mitochondria, Fe/S cluster, IBA57

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Chicago
VANLANDER, ARNAUD, Claudia Willbrecht, Nikhita Ajit Bolar, Joél Smet, Boel De Paepe, ELIEN DE LATTER, Lut Van Laer, Bart Loeys, Roland Lill, and Rudy Van Coster. 2013. “A Homozygous Mutation in IBA57 Involved in Intramitochondrial Iron-sulfur Cluster Synthesis Causes Severe Encephalopathy and Mypathy in Two Neonates.” In European Journal of Paediatric Neurology, 17:S5–S6.
APA
VANLANDER, A., Willbrecht, C., Ajit Bolar, N., Smet, J., De Paepe, B., DE LATTER, E., Van Laer, L., et al. (2013). A homozygous mutation in IBA57 involved in intramitochondrial iron-sulfur cluster synthesis causes severe encephalopathy and mypathy in two neonates. EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY (Vol. 17, pp. S5–S6). Presented at the 10th European Paediatric Neurology Society congress (EPNS 2013).
Vancouver
1.
VANLANDER A, Willbrecht C, Ajit Bolar N, Smet J, De Paepe B, DE LATTER E, et al. A homozygous mutation in IBA57 involved in intramitochondrial iron-sulfur cluster synthesis causes severe encephalopathy and mypathy in two neonates. EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY. 2013. p. S5–S6.
MLA
VANLANDER, ARNAUD, Claudia Willbrecht, Nikhita Ajit Bolar, et al. “A Homozygous Mutation in IBA57 Involved in Intramitochondrial Iron-sulfur Cluster Synthesis Causes Severe Encephalopathy and Mypathy in Two Neonates.” European Journal of Paediatric Neurology. Vol. 17. 2013. S5–S6. Print.
@inproceedings{4233737,
  abstract     = {Background: Combined OXPHOS deficiencies involving complexes I and II have recently been detected in patients with deficient iron-sulfur cluster (ISC) biogenesis. So far, patients were reported with pathogenic mutations in NFU1 and BOLA3 presenting with severe encephalomyopathy at young age.
Objective: Two siblings with combined deficiency of complex I and II were investigated for possible defect in ISC.
Patients and methods: The siblings presented soon after birth with severe encephalomyopathy and died in the neonatal period. Biochemical investigations showed increased lactate in serum and increased glycine in CSF. Considering the consanguineous descent a search for genes in homozygous regions related to ISC metabolism was performed.
Results: Isolating IBA57 as a strong candidate gene, sequencing detected a homozygous mutation (c.941A{\textrangle}C) in the two siblings and a heterozygous carrier status in both parents. Western blotting showed a severe decrease of CRM for the IBA57 protein. The protein amount in the complexes I and II was significantly decreased. Transfection experiments in HeLa cells demonstrated that the mutation was pathogenic and that excessive degradation of the IBA57 protein was responsible for the defective ISC biosynthesis.
Conclusion: This is the first report of a pathogenic mutation in IBA57 in human.},
  articleno    = {abstract O16-1908},
  author       = {Vanlander, Arnaud and Willbrecht, Claudia and Ajit Bolar, Nikhita and Smet, Jo{\'e}l and De Paepe, Boel and De Latter, Elien and Van Laer, Lut and Loeys, Bart and Lill, Roland and Van Coster, Rudy},
  booktitle    = {EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY},
  issn         = {1090-3798},
  language     = {eng},
  location     = {Brussels, Belgium},
  number       = {suppl. 1},
  pages        = {abstract O16-1908:S5--abstract O16-1908:S6},
  title        = {A homozygous mutation in IBA57 involved in intramitochondrial iron-sulfur cluster synthesis causes severe encephalopathy and mypathy in two neonates},
  url          = {http://dx.doi.org/10.1016/S1090-3798(13)70018-7},
  volume       = {17},
  year         = {2013},
}

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