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Congenital Central Hypoventilation Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Expressed during neural development in the nuclei of brainstem areas that contain pathways controlling breathing and auditory functions [5], PHOX2B is regulated transcriptionally by itself, as well as E2a and Hand2 at specific sympathetic and enteric nervous system developmental stages. Other proteins that may play a possible role in the regulation of PHOX2B are SOX10, PHOX2A, and HASH1. Further, by forming trimer with Pbx1 and Meis1, Hoxb1 and Hoxb2 also contribute to the regulation of PHOX2B transcription.
Effects of Retinoids at the Cellular Level (Differentiation, Apoptosis, Autophagy, Cell Cycle Regulation, and Senescence)
Published in Ayse Serap Karadag, Berna Aksoy, Lawrence Charles Parish, Retinoids in Dermatology, 2019
Genes activated by RA are members of different signaling pathways including TGF-β pathway (genes left-right determination factor 2 [LEFTY2], BMP and activin membrane bound inhibitor [BAMBI], Follistatin [FST]), homeodomain pathway (genes HoxD1, MEIS1, MEIS2), gastrulation brain homeobox 2 (GBX2), insulin growth factor (IGF) pathway (genes IGFBP3, IGFBP6, CTGF), Notch pathway (genes manic fringe [MFNG] and metallopeptidase domain 11 [ADAM11]), Hedgehog pathway (gene Patched [PTCH]) and Wnt pathway (genes FRAT2 and secreted frizzled-related protein 1 [SFRP1]) (19). In addition, transcription factors from Sry-related HMG box (SOX) gene family are upregulated during the RA induced neural differentiation, such as SOX3, one of the earliest neural markers (28). It has been postulated that cumulative regulation of SOX target genes during neurogenesis is the result of a fine balance between gene expression control regulated by members of SOXB1 (SOX1, SOX2, SOX3) and SOXB2 (SOX14 and SOX21) gene subfamilies (29–31). The increase in SOXB2 protein levels activates proneural proteins, which subsequently interfere with SOXB1 function, leading to differentiation of a neural progenitor towards neuronal phenotype (29). Members of SOXB subfamily are directly (32–34) and indirectly (35–37) regulated by RA and RA effector signaling. SOXB protein expression changes during the course of differentiation (20), which makes them a group of genes that participate in RA mediated proliferation-differentiation switches.
Congenital thrombocytopenia associated with a heterozygous variant in the MEIS1 gene encoding a transcription factor essential for megakaryopoiesis
Published in Platelets, 2022
Orna Steinberg-Shemer, Naama Orenstein, Tanya Krasnov, Sharon Noy-Lotan, Nathaly Marcoux, Orly Dgany, Joanne Yacobovich, Oded Gilad, Evelyn Shabad, Lina Basel-Salmon, Hannah Tamary
A deletion of MEIS1 in zebrafish and mouse models, and also in human iPSCs, revealed the essential roles of MEIS1 in megakaryopoiesis. The mouse models showed that a homozygous deletion is required to generate a phenotype in the hematopoietic system, while heterozygous mice are normal [4]. In contrast, in the human iPSC model, the heterozygous state showed a partial phenotype [12]. The patient we present had a heterozygous variant in the MEIS1 gene. Her platelet counts improved after the first months of life. This is compatible with an intermediate phenotype as suggested by the human iPSC model [12]. It is not clear why the platelet counts were extremely low after birth and improved thereafter. Identification of additional patients with MEIS1 variants may shed light on this interesting phenomenon. In addition, repeat bone marrow examinations in the future, if indicated, may reveal changes in megakaryocyte number and morphology over time, and their correlations with platelet counts in the peripheral blood. To note, we found in Decipher, seven patients with chromosomal abnormalities that included a deletion in the area of the MEIS1 gene. However, it is not mentioned whether these patients had thrombocytopenia.