Imperial College London
Portrait Picture

ProfessorJulianGriffin

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Visiting Professor
 
 
 
//

Contact

 

+44 (0)20 7594 3220julian.griffin

 
 
//

Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Perrotta:2020:10.1056/NEJMoa1907362,
author = {Perrotta, S and Roberti, D and Bencivenga, D and Corsetto, P and O'Brien, KA and Caiazza, M and Stampone, E and Allison, L and Fleck, RA and Scianguetta, S and Tartaglione, I and Robbins, PA and Casale, M and West, JA and Franzini-Armstrong, C and Griffin, JL and Rizzo, AM and Sinisi, AA and Murray, AJ and Borriello, A and Formenti, F and Della, Ragione F},
doi = {10.1056/NEJMoa1907362},
journal = {New England Journal of Medicine},
pages = {835--844},
title = {Effects of germline VHL deficiency on growth, metabolism, and mitochondria.},
url = {http://dx.doi.org/10.1056/NEJMoa1907362},
volume = {382},
year = {2020}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.).
AU  - Perrotta,S
AU  - Roberti,D
AU  - Bencivenga,D
AU  - Corsetto,P
AU  - O'Brien,KA
AU  - Caiazza,M
AU  - Stampone,E
AU  - Allison,L
AU  - Fleck,RA
AU  - Scianguetta,S
AU  - Tartaglione,I
AU  - Robbins,PA
AU  - Casale,M
AU  - West,JA
AU  - Franzini-Armstrong,C
AU  - Griffin,JL
AU  - Rizzo,AM
AU  - Sinisi,AA
AU  - Murray,AJ
AU  - Borriello,A
AU  - Formenti,F
AU  - Della,Ragione F
DO  - 10.1056/NEJMoa1907362
EP  - 844
PY  - 2020///
SN  - 0028-4793
SP  - 835
TI  - Effects of germline VHL deficiency on growth, metabolism, and mitochondria.
T2  - New England Journal of Medicine
UR  - http://dx.doi.org/10.1056/NEJMoa1907362
UR  - https://www.ncbi.nlm.nih.gov/pubmed/32101665
UR  - https://www.nejm.org/doi/10.1056/NEJMoa1907362
UR  - http://hdl.handle.net/10044/1/82232
VL  - 382
ER  -
Download