Atypical Case Of Wolfram Syndrome Revealed Through Targeted Exome Sequencing In A Patient With Suspected Mitochondrial Disease

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Atypical Case Of Wolfram Syndrome Revealed Through Targeted Exome Sequencing In A Patient With Suspected Mitochondrial Disease

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dc.contributor.author Horton, Laura C
dc.contributor.author Slate, Nancy G
dc.contributor.author Liu, Shangtao
dc.contributor.author Lieber, Daniel Solomon
dc.contributor.author Vafai, Scott Bradley
dc.contributor.author Borowsky, Mark L
dc.contributor.author Calvo, Sarah E
dc.contributor.author Schmahmann, Jeremy Dan
dc.contributor.author Mootha, Vamsi Krishna
dc.date.accessioned 2012-03-29T17:57:12Z
dc.date.issued 2012
dc.identifier.citation Lieber, 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.issn 1471-2350 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:8462353
dc.description.abstract Background: 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.iso en_US en_US
dc.publisher BioMed Central en_US
dc.relation.isversionof doi://10.1186/1471-2350-13-3 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281774/pdf/ en_US
dash.license LAA
dc.title Atypical Case Of Wolfram Syndrome Revealed Through Targeted Exome Sequencing In A Patient With Suspected Mitochondrial Disease en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal BMC Medical Genetics en_US
dash.depositing.author Schmahmann, Jeremy Dan
dc.date.available 2012-03-29T17:57:12Z

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