The patient underwent radiological examinations, including <sup>18</sup> F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT), bone scintigraphy and CT. A biopsy from the lesion with the highest FDG accumulation confirmed the presence of foamy macrophages, a diagnostic clue for ECD.
In the following, four hub genes which were USP7, hepatoma-derived growth factor, EP300, and split hand/foot malformation type 1 (SHFM1) were screened out.None of them was DEGs.
We found a marked increase in CCL18 but not TGF-β1 levels in serum and lesions of ECD patients (<i>p < 0.001</i>), independently of treatment status and consistently over time.
These findings suggest the involvement of CCL18-induced fibrosis in ECD pathogenesis, providing a rationale for exploring CCL18 inhibition as a treatment for progressive fibrosis in ECD.
In the following, four hub genes which were USP7, hepatoma-derived growth factor, EP300, and split hand/foot malformation type 1 (SHFM1) were screened out.None of them was DEGs.
ECD significantly increased the expression of mitochondria-dependent apoptotic pathway-related genes after 48h; we observed significantly (p≤0.05) increased expression of CYP1A, GPX, GSK3β and TNF-α and downregulated expression of NF-κB.
This is the first report of mutations in a human disease with ectrodactyly with pulmonary acinar dysplasia and, as such, homozygous loss-of-function FGFR2 mutations represent a unique syndrome.
Additionally, a literature review allowed us to conclude that KAL1 protein at high levels may interfere with FGFR1 signaling activity, most probably indirectly giving rise to ectrodactyly, intellectual disability, and genital anomalies.
Furthermore, Fc-CLEC2(ECD) treatment improves cytokine profiles and increases both the M2 macrophage population and the genes involved in the oxidation of lipid metabolism in the liver.
Increased expression of PD-L1 (≥2+/≥5%) was seen in 3/4 ECD, 7/8 LCH, 3/3 FDCS and 1/1 HS, with overall 81% concordance between 2 antibodies used in the study (SP142 vs. MAB1561 clone).
There was 100% concordance between tissue and urinary cfDNA genotype in treatment-naïve samples. cfDNA analysis facilitated identification of previously undescribed KRAS(G12S)-mutant ECD and dynamically tracked disease burden in patients treated with a variety of therapies.
Data shown here provides further evidence for the contribution of DLX5 point mutations to the development of ectrodactyly and suggest the possibility of sex-related segregation distortion with an excess of affected males.
In this issue of Blood, the findings of Chakraborty et al and Emile et al support a model in which the mitogen-activated protein kinase (MAPK) and PI3K/AKT pathways are critical in the pathogenesis of 2 of the most common histiocytoses—Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD)—whereas their respective mutational profiles demonstrate important similarities and differences.
Despite the fact that CdCl(2) induced both p53-dependent (in the mesenchyme) and p53-independent (in the AER) cell death in the developing limb bud, CdCl(2)-induced ectrodactyly was independent of the p53 gene dosage at the studied time point.
The second breakpoint associated with holoprosencephaly, hypertelorism and ectrodactyly syndrome was mapped 2.5 Mb proximal at 118.4 Mb and the candidate genes identified from this region were the insulin-induced protein 2 and the homeobox protein engrailed-1.