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Congenital Cranial Dysinnervation Disorder
Published in Vivek Lal, A Clinical Approach to Neuro-Ophthalmic Disorders, 2023
CHN1 gene is responsible for encoding signaling molecule α2-chimaerin and its mutation, or overexpression of wild-type α2-chimaerin results in stalling of axons of third cranial nerve with aberrant branching. Mutation of CHN1 gene can result in familial or isolated DRS. SALL4 is another identified gene in Duane's phenotype. HOXA1 genes are responsible for transcription encoding which is critical for hindbrain development and its mutation results in bilateral DRS, deafness, and autism (8, 19, 20).
Individual conditions grouped according to the international nosology and classification of genetic skeletal disorders*
Published in Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow, Fetal and Perinatal Skeletal Dysplasias, 2012
Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow
Genetics: autosomal dominant, almost complete penetrance; mutations in the gene TBX5 can be found in roughly 70% of patients; in a few cases mutations in the gene SALL4 have been identified. TBX5 is a member of the T-box family of transcription factors and is involved in specification of cardiac and forelimb structures during embryogenesis. TBX5 interacts with NKX2.5 and GATA4 in regulating cardiogenesis, particularly in cardiac septation, and is involved in the development of the cardiac conduction system. SALL4 encodes the sal-like protein 4, which contains 3 C2H2 double zinc finger domains of the SAL-type. Sal-like protein 4 is essential for the development of the epiblast and primitive endoderm from the inner embryonic cell mass. It interacts with SALL1 in anorectal, heart, brain and renal development and with TBX5 in patterning and morphogenesis of the first digit of the upper limbs. Other conditions caused by mutations in SALL4 are Duane radial ray syndrome and acro-renal-ocular syndrome (AROS).
SALL4-mediated upregulation of exosomal miR-146a-5p drives T-cell exhaustion by M2 tumor-associated macrophages in HCC
Published in OncoImmunology, 2019
Chunlai Yin, Qiuju Han, Dongqing Xu, Bingqing Zheng, Xuemei Zhao, Jian Zhang
Our previous study suggested that STAT3 could control the expression of miR-146a-5p in human HCC.39 Here, we found another factor, SALL4, which is reactivated in human HCC and correlates with disease progression of human malignancy and treatment status,61 regulated miR-146a-5p. Previous study demonstrated that SALL4 to be inseparable from malignant proliferation of tumor cells, and was regulated by the transcription factor STAT3.27 Here, we found that SALL4 could directly regulate the expression of miR-146a-5p in HCC cells, silencing SALL4 alleviated the generation of miR-146a-5p and M2-polarization (Figure 5), and markedly improved the outcome of HCC in mice (Figure 6). SALL4 is downstream of STAT3, and its binding sequences in the miR-146a-5p promoter overlapped with STAT3 binding sequences. In addition, silencing SALL4 and STAT3 showed similar effects on the transcriptional activity of miR-146a-5p promoter (data not shown). These findings indicated the possibility that SALL4-STAT3 control miR-146a-5p expression cooperatively.
SALL4 oncogene is an immunogenic antigen presented in various HLA-DR contexts
Published in OncoImmunology, 2018
Marie Kroemer, Laurie Spehner, Patricia Mercier-Letondal, Laura Boullerot, Stefano Kim, Marine Jary, Jeanne Galaine, Emilie Picard, Christophe Ferrand, Thierry Nguyen, Fabrice Larosa, Olivier Adotévi, Yann Godet, Christophe Borg
SALL4, which functions as a driver of stem cell homeostasis, is widely expressed in various solid and hematological malignancies. During natural development, its expression gradually decreases with tissue differentiation status, to finally become marginal in somatic tissue and restricted to germinal, adipose and hematological stem cells. At the time of early development, SALL4 deficiency results in embryonic lethality. Actually, SALL4 appeared to be a major transcription factor that maintains self-renewal and pluripotency of stem cells but also cancer stem cells.30, 31 SALL4 possesses some characteristics of an ideal tumor antigen, supporting its potential use as a target for cancer therapy or as a cancer biomarker. We therefore investigated its immunogenicity using the reverse antigen identification strategy. A large pre-existing T-cell repertoire in healthy donors and cancer patients was found. Our results led to the identification of two immunoprevalent SALL4-derived peptides (A18 K and R18 A). The promiscuous binding of these peptides among different HLA-DR proteins will promote the development of specific immunomonitoring protocols to better decipher the role of SALL4 immunity. Finally, using an A18 K specific T-cell clone we demonstrated that A18 K peptide could be naturally processed and presented by moDC.
Expression pattern and prognostic implication of SALL4 gene in myeloid leukemias: a case-control study
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2019
Hala M. Farawela, Hamdy M. Zawam, Hanan A. Al-Wakeel, Mona H. El-Nagdy, Fatma A. El-Refaey, Hala A. Abdel-Rahman
SALL4 is an embryonic stem cell gene that encodes a transcription factor. It modulates stem cell pluripotency as its expression is down-regulated during development; however, it is aberrantly re-expressed in malignant cells [28]. SALL4 was firstly studied in solid tumors and it was considered as a valid diagnostic marker with a good sensitivity [8,9,29]. Moreover, its role in leukemogenesis is highlighted in different studies [5,6,30]. However, its role as prognostic marker and as molecular target has been recently considered for investigation.