Effects of Germline VHL Deficiency on Growth, Metabolism, and Mitochondria. Perrotta, S., Roberti, D., Bencivenga, D., Corsetto, P., O'Brien, K. A., Caiazza, M., Stampone, E., Allison, L., Fleck, R. A., Scianguetta, S., Tartaglione, I., Robbins, P. A., Casale, M., West, J. A., Franzini-Armstrong, C., Griffin, J. L., Rizzo, A. M., Sinisi, A. A., Murray, A. J., Borriello, A., Formenti, F., & Della Ragione, F. The New England Journal of Medicine, 382(9):835–844, February, 2020. doi abstract bibtex Mutations in VHL, which encodes von Hippel-Lindau tumor suppressor (VHL), are associated with divergent diseases. We describe a patient with marked erythrocytosis and prominent mitochondrial alterations associated with a severe germline VHL deficiency due to homozygosity for a novel synonymous mutation (c.222C→A, p.V74V). The condition is characterized by early systemic onset and differs from Chuvash polycythemia (c.598C→T) in that it is associated with a strongly reduced growth rate, persistent hypoglycemia, and limited exercise capacity. We report changes in gene expression that reprogram carbohydrate and lipid metabolism, impair muscle mitochondrial respiratory function, and uncouple oxygen consumption from ATP production. Moreover, we identified unusual intermitochondrial connecting ducts. Our findings add unexpected information on the importance of the VHL-hypoxia-inducible factor (HIF) axis to human phenotypes. (Funded by Associazione Italiana Ricerca sul Cancro and others.).
@article{perrotta_effects_2020,
title = {Effects of {Germline} {VHL} {Deficiency} on {Growth}, {Metabolism}, and {Mitochondria}},
volume = {382},
issn = {1533-4406},
doi = {10.1056/NEJMoa1907362},
abstract = {Mutations in VHL, which encodes von Hippel-Lindau tumor suppressor (VHL), are associated with divergent diseases. We describe a patient with marked erythrocytosis and prominent mitochondrial alterations associated with a severe germline VHL deficiency due to homozygosity for a novel synonymous mutation (c.222C→A, p.V74V). The condition is characterized by early systemic onset and differs from Chuvash polycythemia (c.598C→T) in that it is associated with a strongly reduced growth rate, persistent hypoglycemia, and limited exercise capacity. We report changes in gene expression that reprogram carbohydrate and lipid metabolism, impair muscle mitochondrial respiratory function, and uncouple oxygen consumption from ATP production. Moreover, we identified unusual intermitochondrial connecting ducts. Our findings add unexpected information on the importance of the VHL-hypoxia-inducible factor (HIF) axis to human phenotypes. (Funded by Associazione Italiana Ricerca sul Cancro and others.).},
language = {eng},
number = {9},
journal = {The New England Journal of Medicine},
author = {Perrotta, Silverio and Roberti, Domenico and Bencivenga, Debora and Corsetto, Paola and O'Brien, Katie A. and Caiazza, Martina and Stampone, Emanuela and Allison, Leanne and Fleck, Roland A. and Scianguetta, Saverio and Tartaglione, Immacolata and Robbins, Peter A. and Casale, Maddalena and West, James A. and Franzini-Armstrong, Clara and Griffin, Julian L. and Rizzo, Angela M. and Sinisi, Antonio A. and Murray, Andrew J. and Borriello, Adriana and Formenti, Federico and Della Ragione, Fulvio},
month = feb,
year = {2020},
pmid = {32101665},
pages = {835--844},
}
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We describe a patient with marked erythrocytosis and prominent mitochondrial alterations associated with a severe germline VHL deficiency due to homozygosity for a novel synonymous mutation (c.222C→A, p.V74V). The condition is characterized by early systemic onset and differs from Chuvash polycythemia (c.598C→T) in that it is associated with a strongly reduced growth rate, persistent hypoglycemia, and limited exercise capacity. We report changes in gene expression that reprogram carbohydrate and lipid metabolism, impair muscle mitochondrial respiratory function, and uncouple oxygen consumption from ATP production. Moreover, we identified unusual intermitochondrial connecting ducts. Our findings add unexpected information on the importance of the VHL-hypoxia-inducible factor (HIF) axis to human phenotypes. 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(Funded by Associazione Italiana Ricerca sul Cancro and others.).},\n\tlanguage = {eng},\n\tnumber = {9},\n\tjournal = {The New England Journal of Medicine},\n\tauthor = {Perrotta, Silverio and Roberti, Domenico and Bencivenga, Debora and Corsetto, Paola and O'Brien, Katie A. and Caiazza, Martina and Stampone, Emanuela and Allison, Leanne and Fleck, Roland A. and Scianguetta, Saverio and Tartaglione, Immacolata and Robbins, Peter A. and Casale, Maddalena and West, James A. and Franzini-Armstrong, Clara and Griffin, Julian L. and Rizzo, Angela M. and Sinisi, Antonio A. and Murray, Andrew J. and Borriello, Adriana and Formenti, Federico and Della Ragione, Fulvio},\n\tmonth = feb,\n\tyear = {2020},\n\tpmid = {32101665},\n\tpages = {835--844},\n}\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n","author_short":["Perrotta, S.","Roberti, D.","Bencivenga, D.","Corsetto, P.","O'Brien, K. A.","Caiazza, M.","Stampone, E.","Allison, L.","Fleck, R. 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