Academic Journal
Recessive pathogenic variants in MCAT cause combined oxidative phosphorylation deficiency
| العنوان: | Recessive pathogenic variants in MCAT cause combined oxidative phosphorylation deficiency |
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| المؤلفون: | Webb, Bryn D, Nowinski, Sara M, Solmonson, Ashley, Ganesh, Jaya, Rodenburg, Richard J, Leandro, Joao, Evans, Anthony, Vu, Hieu S, Naidich, Thomas P, Gelb, Bruce D, DeBerardinis, Ralph J, Rutter, Jared, Houten, Sander M |
| المساهمون: | Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of General Medical Sciences, The Nora Eccles Treadwell Foundation, Howard Hughes Medical Institute, National Cancer Institute, The Once Upon a Time Foundation, National Heart, Lung, and Blood Institute |
| المصدر: | eLife ; volume 12 ; ISSN 2050-084X |
| بيانات النشر: | eLife Sciences Publications, Ltd |
| سنة النشر: | 2023 |
| المجموعة: | eLife (E-Journal - via CrossRef) |
| الوصف: | Malonyl-CoA-acyl carrier protein transacylase (MCAT) is an enzyme involved in mitochondrial fatty acid synthesis (mtFAS) and catalyzes the transfer of the malonyl moiety of malonyl-CoA to the mitochondrial acyl carrier protein (ACP). Previously, we showed that loss-of-function of mtFAS genes, including Mcat , is associated with severe loss of electron transport chain (ETC) complexes in mouse immortalized skeletal myoblasts (Nowinski et al., 2020). Here, we report a proband presenting with hypotonia, failure to thrive, nystagmus, and abnormal brain MRI findings. Using whole exome sequencing, we identified biallelic variants in MCAT . Protein levels for NDUFB8 and COXII, subunits of complex I and IV respectively, were markedly reduced in lymphoblasts and fibroblasts, as well as SDHB for complex II in fibroblasts. ETC enzyme activities were decreased in parallel. Re-expression of wild-type MCAT rescued the phenotype in patient fibroblasts. This is the first report of a patient with MCAT pathogenic variants and combined oxidative phosphorylation deficiency. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.7554/elife.68047 |
| الاتاحة: | http://dx.doi.org/10.7554/elife.68047 https://cdn.elifesciences.org/articles/68047/elife-68047-v1.pdf https://cdn.elifesciences.org/articles/68047/elife-68047-v1.xml https://elifesciences.org/articles/68047 |
| Rights: | http://creativecommons.org/licenses/by/4.0/ ; http://creativecommons.org/licenses/by/4.0/ ; http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.70528446 |
| قاعدة البيانات: | BASE |
| DOI: | 10.7554/elife.68047 |
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