Expanding the phenotypic and molecular spectrum of NFS1-related disorders that cause functional deficiencies in mitochondrial and cytosolic iron-sulfur cluster containing enzymes
| العنوان: | Expanding the phenotypic and molecular spectrum of NFS1-related disorders that cause functional deficiencies in mitochondrial and cytosolic iron-sulfur cluster containing enzymes |
|---|---|
| المؤلفون: | Jennifer H. Yang, Marisa W. Friederich, Katarzyna A. Ellsworth, Aliya Frederick, Emily Foreman, Denise Malicki, David Dimmock, Jerica Lenberg, Chitra Prasad, Andrea C. Yu, C. Anthony Rupar, Robert A. Hegele, Kandamurugu Manickam, Daniel C. Koboldt, Erin Crist, Samantha S. Choi, Sali M.K. Farhan, Helen Harvey, Shifteh Sattar, Natalya Karp, Terence Wong, Richard Haas, Johan L. K. Van Hove, Kristen Wigby |
| المصدر: | Human mutation, vol 43, iss 3 Hum Mutat |
| بيانات النشر: | eScholarship, University of California, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Iron-Sulfur Proteins, Pediatric, Genetics & Heredity, Electron Transport Complex I, iron-sulfur clusteropathies, Iron, Clinical Sciences, NFS1, mitochondrial, Article, Mitochondria, Mitochondrial Proteins, Carbon-Sulfur Lyases, Young Adult, lactic acidosis, Clinical Research, Genetics, Humans, 2.1 Biological and endogenous factors, Aetiology, Genetics (clinical), Sulfur |
| الوصف: | Iron-sulfur cluster proteins are involved in critical functions for gene expression regulation and mitochondrial bioenergetics including the oxidative phosphorylation system. The c.215G>A p.(Arg72Gln) variant in NFS1 has been previously reported to cause infantile mitochondrial complex II and III deficiency. We describe three additional unrelated patients with the same missense variant. Two infants with the same homozygous variant presented with hypotonia, weakness and lactic acidosis, and one patient with compound heterozygous p.(Arg72Gln) and p.(Arg412His) variants presented as a young adult with gastrointestinal symptoms and fatigue. Skeletal muscle biopsy from patients 1 and 3 showed abnormal mitochondrial morphology, and functional analyses demonstrated decreased activity in respiratory chain complex II and variably in complexes I and III. We found decreased mitochondrial and cytosolic aconitase activities but only mildly affected lipoylation of pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase enzymes. Our studies expand the phenotypic spectrum and provide further evidence for the pathogenicity and functional sequelae of NFS1-related disorders with disturbances in both mitochondrial and cytosolic iron-sulfur cluster containing enzymes. |
| وصف الملف: | application/pdf |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e645f94902b36d211d5a0a320945ef4f https://escholarship.org/uc/item/68j1p63k |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e645f94902b36d211d5a0a320945ef4f |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |