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dc.contributor.authorLieber, Daniel Solomon
dc.contributor.authorVafai, Scott Bradley
dc.contributor.authorHorton, Laura C
dc.contributor.authorSlate, Nancy G
dc.contributor.authorLiu, Shangtao
dc.contributor.authorBorowsky, Mark L
dc.contributor.authorCalvo, Sarah E
dc.contributor.authorSchmahmann, Jeremy Dan
dc.contributor.authorMootha, Vamsi Krishna
dc.date.accessioned2012-03-29T17:57:12Z
dc.date.issued2012
dc.identifier.citationLieber, Daniel S, Scott B. Vafai, Laura C. Horton, Nancy G. Slate, Shangtao Liu, Mark L. Borowsky, Sarah E. Calvo, Jeremy D. Schmahmann, and Vamsi K. Mootha. 2012. Atypical case of Wolfram syndrome revealed through targeted exome sequencing in a patient with suspected mitochondrial disease. BMC Medical Genetics 13: 3.en_US
dc.identifier.issn1471-2350en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:8462353
dc.description.abstractBackground: Mitochondrial diseases comprise a diverse set of clinical disorders that affect multiple organ systems with varying severity and age of onset. Due to their clinical and genetic heterogeneity, these diseases are difficult to diagnose. We have developed a targeted exome sequencing approach to improve our ability to properly diagnose mitochondrial diseases and apply it here to an individual patient. Our method targets mitochondrial DNA (mtDNA) and the exons of 1,600 nuclear genes involved in mitochondrial biology or Mendelian disorders with multi-system phenotypes, thereby allowing for simultaneous evaluation of multiple disease loci. Case Presentation: Targeted exome sequencing was performed on a patient initially suspected to have a mitochondrial disorder. The patient presented with diabetes mellitus, diffuse brain atrophy, autonomic neuropathy, optic nerve atrophy, and a severe amnestic syndrome. Further work-up revealed multiple heteroplasmic mtDNA deletions as well as profound thiamine deficiency without a clear nutritional cause. Targeted exome sequencing revealed a homozygous c.1672C > T (p.R558C) missense mutation in exon 8 of WFS1 that has previously been reported in a patient with Wolfram syndrome. Conclusion: This case demonstrates how clinical application of next-generation sequencing technology can enhance the diagnosis of patients suspected to have rare genetic disorders. Furthermore, the finding of unexplained thiamine deficiency in a patient with Wolfram syndrome suggests a potential link between WFS1 biology and thiamine metabolism that has implications for the clinical management of Wolfram syndrome patients.en_US
dc.language.isoen_USen_US
dc.publisherBioMed Centralen_US
dc.relation.isversionofdoi://10.1186/1471-2350-13-3en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281774/pdf/en_US
dash.licenseLAA
dc.titleAtypical Case Of Wolfram Syndrome Revealed Through Targeted Exome Sequencing In A Patient With Suspected Mitochondrial Diseaseen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalBMC Medical Geneticsen_US
dash.depositing.authorSchmahmann, Jeremy Dan
dc.date.available2012-03-29T17:57:12Z
dc.identifier.doi10.1186/1471-2350-13-3*
dash.contributor.affiliatedLieber, Daniel Solomon
dash.contributor.affiliatedVafai, Scott B.
dash.contributor.affiliatedCalvo, Sarah
dash.contributor.affiliatedBorowsky, Mark L
dash.contributor.affiliatedSchmahmann, Jeremy
dash.contributor.affiliatedMootha, Vamsi


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