کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8398926 | 1544407 | 2017 | 29 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Recessive mutation in EXOSC3 associates with mitochondrial dysfunction and pontocerebellar hypoplasia
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیوفیزیک
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Recessive mutation in EXOSC3 associates with mitochondrial dysfunction and pontocerebellar hypoplasia Recessive mutation in EXOSC3 associates with mitochondrial dysfunction and pontocerebellar hypoplasia](/preview/png/8398926.png)
چکیده انگلیسی
Recessive mutations in EXOSC3, encoding a subunit of the human RNA exosome complex, cause pontocerebellar hypoplasia type 1b (PCH1B). We report a boy with severe muscular hypotonia, psychomotor retardation, progressive microcephaly, and cerebellar atrophy. Biochemical abnormalities comprised mitochondrial complex I and pyruvate dehydrogenase complex (PDHc) deficiency. Whole exome sequencing uncovered a known EXOSC3 mutation p.(D132A) as the underlying cause. In patient fibroblasts, a large portion of the EXOSC3 protein was trapped in the cytosol. MtDNA copy numbers in muscle were reduced to 35%, but mutations in the mtDNA and in nuclear mitochondrial genes were ruled out. RNA-Seq of patient muscle showed highly increased mRNA copy numbers, especially for genes encoding structural subunits of OXPHOS complexes I, III, and IV, possibly due to reduced degradation by a dysfunctional exosome complex. This is the first case of mitochondrial dysfunction associated with an EXOSC3 mutation, which expands the phenotypic spectrum of PCH1B. We discuss the links between exosome and mitochondrial dysfunction.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Mitochondrion - Volume 37, November 2017, Pages 46-54
Journal: Mitochondrion - Volume 37, November 2017, Pages 46-54
نویسندگان
Gudrun Schottmann, Sylvie Picker-Minh, Jana Marie Schwarz, Esther Gill, Richard J.T. Rodenburg, Werner Stenzel, Angela M. Kaindl, Markus Schuelke,