Authors
Gali Heimer, Juha M Kerätär, Lisa G Riley, Shanti Balasubramaniam, Eran Eyal, Laura P Pietikäinen, J Kalervo Hiltunen, Dina Marek-Yagel, Jeffrey Hamada, Allison Gregory, Caleb Rogers, Penelope Hogarth, Martha A Nance, Nechama Shalva, Alvit Veber, Michal Tzadok, Andreea Nissenkorn, Davide Tonduti, Florence Renaldo, Michael J Bamshad, Suzanne M Leal, Deborah A Nickerson, Peter Anderson, Marcus Annable, Elizabeth Marchani Blue, Kati J Buckingham, Jennifer Chin, Jessica X Chong, Rodolfo Cornejo, Colleen P Davis, Christopher Frazar, Zongxiao He, Gail P Jarvik, Guillaume Jimenez, Eric Johanson, Tom Kolar, Stephanie A Krauter, Daniel Luksic, Colby T Marvin, Sean McGee, Daniel J McGoldrick, Karynne Patterson, Marcos Perez, Sam W Phillips, Jessica Pijoan, Peggy D Robertson, Regie Santos-Cortez, Aditi Shankar, Krystal Slattery, Kathryn M Shively, Deborah L Siegel, Joshua D Smith, Monica Tackett, Gao Wang, Marc Wegener, Jeffrey M Weiss, Riana I Wernick, Marsha M Wheeler, Qian Yi, Ichraf Kraoua, Celeste Panteghini, Lorella Valletta, Barbara Garavaglia, Mark J Cowley, Velimir Gayevskiy, Tony Roscioli, Jonathon M Silberstein, Chen Hoffmann, Annick Raas-Rothschild, Valeria Tiranti, Yair Anikster, John Christodoulou, Alexander J Kastaniotis, Bruria Ben-Zeev, Susan J Hayflick
Publication date
2016/12/1
Journal
The American Journal of Human Genetics
Volume
99
Issue
6
Pages
1229-1244
Publisher
Elsevier
Description
Mitochondrial fatty acid synthesis (mtFAS) is an evolutionarily conserved pathway essential for the function of the respiratory chain and several mitochondrial enzyme complexes. We report here a unique neurometabolic human disorder caused by defective mtFAS. Seven individuals from five unrelated families presented with childhood-onset dystonia, optic atrophy, and basal ganglia signal abnormalities on MRI. All affected individuals were found to harbor recessive mutations in MECR encoding the mitochondrial trans-2-enoyl-coenzyme A-reductase involved in human mtFAS. All six mutations are extremely rare in the general population, segregate with the disease in the families, and are predicted to be deleterious. The nonsense c.855T>G (p.Tyr285∗), c.247_250del (p.Asn83Hisfs∗4), and splice site c.830+2_830+3insT mutations lead to C-terminal truncation variants of MECR. The missense c.695G>A (p …
Scholar articles
G Heimer, JM Kerätär, LG Riley, S Balasubramaniam… - The American Journal of Human Genetics, 2016