Search

Your search keyword '"Vafai, Scott B."' showing total 21 results
Start Over Author "Vafai, Scott B."
21 results on '"Vafai, Scott B."'

13. Atypical case of Wolfram syndrome revealed through targeted exome sequencing in a patient with suspected mitochondrial disease

Author

Lieber Daniel S, Vafai Scott B, Horton Laura C, Slate Nancy G, Liu Shangtao, Borowsky Mark L, Calvo Sarah E, Schmahmann Jeremy D, and Mootha Vamsi K

Subjects
Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

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.

Published
2012
Full Text
View/download PDF

16. Mitochondrial dysfunction remodels one-carbon metabolism in human cells

Author

Massachusetts Institute of Technology. Department of Biology, Regev, Aviv, Bao, Xiaoyan Robert, Ong, Shao-En, Goldberger, Olga, Peng, Jun, Sharma, Rohit, Thompson, Dawn A, Vafai, Scott B, Cox, Andrew G, Marutani, Eizo, Ichinose, Fumito, Goessling, Wolfram, Carr, Steven A, Clish, Clary B, Mootha, Vamsi K, Massachusetts Institute of Technology. Department of Biology, Regev, Aviv, Bao, Xiaoyan Robert, Ong, Shao-En, Goldberger, Olga, Peng, Jun, Sharma, Rohit, Thompson, Dawn A, Vafai, Scott B, Cox, Andrew G, Marutani, Eizo, Ichinose, Fumito, Goessling, Wolfram, Carr, Steven A, Clish, Clary B, and Mootha, Vamsi K

Abstract

Mitochondrial dysfunction is associated with a spectrum of human disorders, ranging from rare, inborn errors of metabolism to common, age-associated diseases such as neurodegeneration. How these lesions give rise to diverse pathology is not well understood, partly because their proximal consequences have not been well-studied in mammalian cells. Here we provide two lines of evidence that mitochondrial respiratory chain dysfunction leads to alterations in one-carbon metabolism pathways. First, using hypothesis-generating metabolic, proteomic, and transcriptional profiling, followed by confirmatory experiments, we report that mitochondrial DNA depletion leads to an ATF4-mediated increase in serine biosynthesis and transsulfuration. Second, we show that lesioning the respiratory chain impairs mitochondrial production of formate from serine, and that in some cells, respiratory chain inhibition leads to growth defects upon serine withdrawal that are rescuable with purine or formate supplementation. Our work underscores the connection between the respiratory chain and one-carbon metabolism with implications for understanding mitochondrial pathogenesis., National Institutes of Health (U.S.) (Grant R01DK081457)

Published
2016

18. Mitochondrial dysfunction remodels one-carbon metabolism in human cells

Author

Bao, Xiaoyan Robert, primary, Ong, Shao-En, additional, Goldberger, Olga, additional, Peng, Jun, additional, Sharma, Rohit, additional, Thompson, Dawn A, additional, Vafai, Scott B, additional, Cox, Andrew G, additional, Marutani, Eizo, additional, Ichinose, Fumito, additional, Goessling, Wolfram, additional, Regev, Aviv, additional, Carr, Steven A, additional, Clish, Clary B, additional, and Mootha, Vamsi K, additional

Published
2016
Full Text
View/download PDF

19. Author response: Mitochondrial dysfunction remodels one-carbon metabolism in human cells

Author

Bao, Xiaoyan Robert, primary, Ong, Shao-En, additional, Goldberger, Olga, additional, Peng, Jun, additional, Sharma, Rohit, additional, Thompson, Dawn A, additional, Vafai, Scott B, additional, Cox, Andrew G, additional, Marutani, Eizo, additional, Ichinose, Fumito, additional, Goessling, Wolfram, additional, Regev, Aviv, additional, Carr, Steven A, additional, Clish, Clary B, additional, and Mootha, Vamsi K, additional

Published
2015
Full Text
View/download PDF

21. Regression of Drug-Resistant Lung Cancer by the Combination of Rosiglitazone and Carboplatin

Author

Girnun, Geoffrey D., primary, Chen, Liang, additional, Silvaggi, Jessica, additional, Drapkin, Ronny, additional, Chirieac, Lucian R., additional, Padera, Robert F., additional, Upadhyay, Rabi, additional, Vafai, Scott B., additional, Weissleder, Ralph, additional, Mahmood, Umar, additional, Naseri, Elnaz, additional, Buckley, Stephanie, additional, Li, Danan, additional, Force, Jeremy, additional, McNamara, Kate, additional, Demetri, George, additional, Spiegelman, Bruce M., additional, and Wong, Kwok-Kin, additional

Published
2008
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results