Search results for "X-linked."
showing 5 items of 65 documents
Excess of de novo variants in genes involved in chromatin remodelling in patients with marfanoid habitus and intellectual disability.
2020
PurposeMarfanoid habitus (MH) combined with intellectual disability (ID) (MHID) is a clinically and genetically heterogeneous presentation. The combination of array CGH and targeted sequencing of genes responsible for Marfan or Lujan–Fryns syndrome explain no more than 20% of subjects.MethodsTo further decipher the genetic basis of MHID, we performed exome sequencing on a combination of trio-based (33 subjects) or single probands (31 subjects), of which 61 were sporadic.ResultsWe identified eight genes with de novo variants (DNVs) in at least two unrelated individuals (ARID1B, ATP1A1, DLG4, EHMT1, NFIX, NSD1, NUP205 and ZEB2). Using simulation models, we showed that five genes (DLG4, NFIX, …
Topotecan triggers apoptosis in p53-deficient cells by forcing degradation of XIAP and survivin thereby activating caspase-3-mediated Bid cleavage.
2009
The topoisomerase I inhibitor topotecan (TPT) is used in the therapy of different tumors including high-grade gliomas. We previously showed that TPT-induced apoptosis depends on p53 with p53 wild-type (wt) cells being more resistant because of p53-controlled degradation of topoisomerase I. Here, we show that p53-deficient (p53(-/-)) fibroblasts undergo excessive mitochondrial apoptosis featuring H2AX phosphorylation, Bcl-x(L) decline, cytochrome c release, caspase-9/-3/-2 activation, and cleavage of Bid. In wt and apaf-1(-/-) cells, caspase-2 did not become activated and Bid was not cleaved. In addition, p53(-/-) cells cotreated with TPT and caspase-3 inhibitor showed neither caspase-2 acti…
X-Linked myopathy with excessive autophagy: A new hereditary muscle disease
1988
We report on 3 brothers with a myopathy that also affected their maternal grandfather and great-uncle. Characteristic features are onset in early childhood, very slow progression, normal life expectancy, weakness of proximal limb muscles, especially in the legs, elevation of serum creatine kinase, and no cardiac or intellectual involvement. In biopsy material muscle fibers are almost never necrotic but show excessive autophagic activity and exocytosis of the phagocytosed material. We suggest that this family has an undescribed type of congenital myopathy, for which we propose the name X-linked myopathy with excessive autophagy.