دورية أكاديمية

Expanding the spectrum of PEX16 mutations and novel insights into disease mechanisms

التفاصيل البيبلوغرافية
العنوان: Expanding the spectrum of PEX16 mutations and novel insights into disease mechanisms
المؤلفون: Kishore R. Kumar, Gautam Wali, Ryan L. Davis, Amali C. Mallawaarachchi, Elizabeth E. Palmer, Velimir Gayevskiy, Andre E. Minoche, David Veivers, Marcel E. Dinger, Alan Mackay-Sim, Mark J. Cowley, Carolyn M. Sue
المصدر: Molecular Genetics and Metabolism Reports, Vol 16, Iss , Pp 46-51 (2018)
بيانات النشر: Elsevier, 2018.
سنة النشر: 2018
المجموعة: LCC:Medicine (General)
LCC:Biology (General)
مصطلحات موضوعية: Medicine (General), R5-920, Biology (General), QH301-705.5
الوصف: Zellweger syndrome spectrum disorders are caused by mutations in any of at least 12 different PEX genes. This includes PEX16, an important regulator of peroxisome biogenesis. Using whole genome sequencing, we detected previously unreported, biallelic variants in PEX16 [NM_004813.2:c.658G>A, p.(Ala220Thr) and NM_004813.2:c.830G>A, p.(Arg277Gln)] in an individual with leukodystrophy, spastic paraplegia, cerebellar ataxia, and craniocervical dystonia with normal plasma very long chain fatty acids. Using olfactory-neurosphere derived cells, a population of neural stem cells, we showed patient cells had reduced peroxisome density and increased peroxisome size, replicating previously reported findings in PEX16 cell lines. Along with alterations in peroxisome morphology, patient cells also had impaired peroxisome function with reduced catalase activity. Furthermore, patient cells had reduced oxidative stress levels after exposure to hydrogen-peroxide (H2O2), which may be a result of compensation by H2O2 metabolising enzymes other than catalase to preserve peroxisome-related cell functions. Our findings of impaired catalase activity and altered oxidative stress response are novel. Our study expands the phenotype of PEX16 mutations by including dystonia and provides further insights into the pathological mechanisms underlying PEX16-associated disorders. Additional studies of the full spectrum of peroxisomal dysfunction could improve our understanding of the mechanism underlying PEX16-associated disorders. Keywords: Whole genome sequencing, PEX16, Peroxisomes, Leukodystrophy, Dystonia
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2214-4269
العلاقة: http://www.sciencedirect.com/science/article/pii/S2214426918300715Test; https://doaj.org/toc/2214-4269Test
DOI: 10.1016/j.ymgmr.2018.07.003
الوصول الحر: https://doaj.org/article/200e2d28977c4ba3868988de70ca5ca7Test
رقم الانضمام: edsdoj.200e2d28977c4ba3868988de70ca5ca7
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:22144269
DOI:10.1016/j.ymgmr.2018.07.003