Journal: Cell Death Discovery

Article Title: Role of RB1 in neurodegenerative diseases: inhibition of post-mitotic neuronal apoptosis via Kmt5b

doi: 10.1038/s41420-024-01955-y

Figure Lengend Snippet: A RB1 mutation rates by DNA sequence data in blood samples from PD (n = 189), AD (n = 33), HD (n = 69), and ALS (n = 75) patients from the Guangzhou KingMed Diagnostics Group Co. B Detailed information of the six mutation sites in neurodegenerative patients. C The detailed frequencies of the six mutation sites in neurodegenerative patients, normal Eastern Asian population, and frequency in the ALAF project from NCBI. PD Parkinson’s disease, AD Alzheimer’s disease, HD Huntington’s disease, ALS amyotrophic lateral sclerosis; -: no data. (Fisher’s exact test; *** P < 0.001).

Article Snippet: To determine the relationship between RB1 mutations and neurodegenerative disease, we calculated the RB1 mutation rates of PD (189 blood samples), AD (33 blood samples), HD (69 blood samples), and ALS (75 blood samples) using DNA sequence data from Guangzhou KingMed Diagnostics Group Co., Ltd.

Techniques: Mutagenesis, Sequencing

Journal: Acta Neuropathologica Communications

Article Title: A novel recessive mutation affecting DNAJB6a causes myofibrillar myopathy

doi: 10.1186/s40478-020-01046-w

Figure Lengend Snippet: Clinical, histopathological and molecular features of the patient with the DNAJB6 mutation. a The pedigree displayed co-segregation of the p.V232Gfs*7 homozygosis mutation (changes in the genotype labeled in red) with distal-onset myopathy. The arrow indicates the proband (individual II-5). Square: male; circle: female; open symbol: unaffected; filled symbol: affected; symbol with a diagonal line: deceased. b Representative chromatogram of the forward sequencing reaction in the proband displayed a novel mutation in DNAJB6 genomic DNA (c.695_699del; p.V232Gfs*7) (the mutation of genome and amino acids labeled in red arrow and dotted frame). c Patient II5: distal lower limb atrophy (white arrows) and bilateral foot drop (black arrows). d MRI revealed generalized fatty replacement in the distal lower legs, and vastus, gracilis, and semitendinosus muscles (black arrows). Substantial muscle alterations with fatty infiltration were observed in paraspinal, infraspinatus, and intercostal muscles (white arrows). e Histochemical analysis of the vastus lateralis muscle biopsy demonstrated the presence of increased connective tissue, pathological variation of fiber diameter, pyknotic nuclear clumps, and rimmed vacuoles (black arrowheads), as shown in hematoxylin & eosin (H&E) staining. Modified Gomori trichrome (MGT) staining displayed sarcoplasmic masses located principally around the rimmed vacuoles. In addition, succinate dehydrogenase (SDH) and cytochrome C oxidase (COX) stains revealed multiple fibers with areas of diminished enzyme staining. Scale bar = 100 µm. f Electron microscopy indicated disruption of Z-disks (white arrows, 1), large electron-dense material located at the perinuclear regions (black arrows, 2), and abnormal mitochondria (white arrowheads, 3). Scale bars = 0.5 µm (1, 3), 1 µm (2). g Confocal microscopy showed that DNAJB6 staining highlighted in multiple fibers with subsarcolemmal accumulation and sarcoplasmic inclusions, while it was absent in myonucleus. Scale bars = 100 µm (1), 20 µm (2). h Confocal microscopy shows desmin co-located with DNAJB6 in muscle cytoplasm (1), p62 (2) and TDP-43 (3) strongly positive in rimmed vacuoles. Scale bar = 100 µm. i Immunohistochemical analysis showed LC3b staining around the rimmed vacuoles and Dysferlin accumulation in the cytoplasm. Scale bar = 100 µm. j RT-qPCR analysis of mRNA expression levels of human-wild type DNAJB6a (h-wt DNAJB6a), human-mutant DNAJB6a (h-mut DNAJB6a), human-DNAJB6b (h-DNAJB6b) and human-total DNAJB6 (h-total DNAJB6) in a muscle biopsy of individual II-5. k Representative Western blot analysis of muscle (30 µg) homogenates from controls and patient II-5, using DNAJB6 and GAPDH antibodies. Note that the h-DNAJB6b band might comprise h-mut DNAJB6a. l Relative quantification of the level of DNAJB6 in II-5 compared with controls demonstrates a clear reduction in DNAJB6. P value = * < 0.05, ** < 0.01

Article Snippet: The 300 in-house Asia database, generated using next-generation sequencing data of DNA from 300 normal Chinese individuals provided by MyGenostics was also used to filter variants.

Techniques: Mutagenesis, Labeling, Sequencing, Muscles, Staining, Modification, Electron Microscopy, Disruption, Confocal Microscopy, Immunohistochemical staining, Quantitative RT-PCR, Expressing, Western Blot, Quantitative Proteomics