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Fanconi Anemia
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Fanconi anemia caused by homozygous or compound heterozygous mutations involving one of 20 FANC genes (FANCA, FANCC, FANCG, FANCD1/BRCA2, FANCD2, FANCE, FANCF, FANCJ, FANCI, FANCL, FANCM, FANCN, FANCO, FANCP, FANCQ, FANCT, FANCU, FANCV, FANCW) demonstrates autosomal recessive inheritance, FA due to heterozygous mutations in FANCR (RAD51) shows autosomal dominant inheritance, and FA resulting from hemizygous mutations in FANCB has X-linked inheritance.
Personalized Medicine in Hereditary Cancer Syndromes
Published in II-Jin Kim, Cancer Genetics and Genomics for Personalized Medicine, 2017
Fanconi anemia is a chromosomal fragility disorder caused by germline mutations in genes essential for repair of DNA interstrand cross-links during replication. The FA DNA repair pathway consists of at least 15 FA gene products. The FA core complex formed by eight FA proteins activates the monoubiquitination of FANCD2 and FANCI. The ubiquitinated FANCD2 interacts with several other proteins and coordinates DNA repair activities (Fig. 10.3) [32, 33]. Patients with FA have defects in FA genes, which impairs the repair activities.
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: a genetically heterogeneous disorder, 13 genes have been identified to date, which define the respective FA complementation groups: FANCA (includes the previously designated FANCH), FANCB, FANCC, FANCD1 (BRCA2), FANCD2, FANCE, FANCF, FANCG (XRCC9), FANCI (KIAA1794), FANCJ (BRIP1), FANCL (PHF9), FANCM, FANCN ( PALB2), and FANCO ( RAD51C). All the FA subtypes are autosomal recessive disorders, except for FANCB which is X-linked. The products of the genes FANC- A, C, E, F, G, L are part of a nuclear complex which regulate the monoubiquitination of FANCD2 during the S phase of the cell cycle or after DNA damage by crosslinking agents (e.g. mitomycin C, diepoxybutane (DEB), cisplatin), which targets FANCD2 to BRCA1 nuclear foci containing BRCA2 (FANCD1) and RAD51. The FA/BRCA pathway (FANCD1-BRCA2, FANCJ-BRIP1, FANCN-PALB2) is implicated in the repair of DNA damage. The diagnosis first relies on the finding of increased chromosomal breakage or rearrangements when a patient’s cell culture is exposed to diepoxybutane (DEB) or radial figures when exposed to mitomycin C (MMC).
Comparison of transcriptome profiles of nucleated red blood cells in cord blood between preterm and full-term neonates
Published in Hematology, 2022
Yuanyuan Han, Ling Huang, Man Zhou, Xiaoyu Tan, Shangjin Gong, Zhaojun Zhang, Tingting Jin, Xiangdong Fang, Yankai Jia, S. W. Huang
After excluding three samples carrying thalassemia mutations, we performed RT-qPCR analysis on the NRBCs isolated from 75 umbilical cord blood samples to verify the differential expression of 14 mRNAs and lncRNAs (Figure 5). Among the 17 genes selected for RT-qPCR, the results of 13 genes were consistent with the transcriptome sequencing results. Compared with the preterm group, the full-term group had higher mRNA expression levels of HBB, BCL11A, ZBTB7A, CA1, HMGB2, JAZF1 (3.52-, 3.24-, 1.45-, 5.07-, 1.59-, and 2.45-fold, respectively) (Figure 5a). The expression levels of Fanconi anemia-related genes, such as FANCA, FANCC, and FANCD2, was 1.36-, 1.35-, and 1.35-fold higher in the full-term group (Figure 5b). The expression levels of H19, LIN28B, and miR-675-3p were 69.98-, 2.38-, and 1.95-fold lower in the full-term group, whereas let-7b-5p was 4.98-fold higher in the full-term group (Figure 5c, d). The results were consistent with those of the RNA-seq. We observed no significant differences in the expression of DANCR, SIRT6, and miR-675-5p, but FANCF was lower in the full-term group (Figure S3e, f). In addition, we found that BCL11A expression significantly differed based on biological sex. The NRBCs from preterm male neonates had 4.25-fold higher expression than that from PF neonates, and full-term male neonates had 2.64-fold higher expression than FF neonates (Figure 5e).
Targetting ferroptosis for blood cell-related diseases
Published in Journal of Drug Targeting, 2022
Zhe Chen, Jinyong Jiang, Nian Fu, Linxi Chen
Additionally, some studies show that ferroptosis mediates anaemia by inducing marrow damage during radiotherapy and chemotherapy. Radiation can reduce fresh bone marrow colony to form haematopoietic progenitor cells, thus suppressing marrow haematopoiesis [77]. A recent study indicates that anti-ferroptosis drug baicalein can further mitigate bone marrow damage induced by total-body irradiation (TBI), anti-apoptotic drug JP4-039 and anti-necrosis drug necrostatin-1 [78]. The three-therapy regimen can alleviate bone marrow damage and further increase the 30-day survival rate to 75% by normalising the preirradiation levels of inflammatory cytokine and the stress response protein levels in plasma. Additionally, fanconi anaemia complementation group D2 (FANCD2) can protect against ferroptosis-mediated injury in bone marrow stromal cells (BMSCs), thereby alleviating DNA damage caused by chemotherapy and radiotherapy [79]. Thus, above evidence may supply novel methods for anaemia treatment, for example, using a blocker of ferroptosis mitigates the radiotherapy-induced and chemotherapy-induced marrow haematopoiesis suppression (Figure 1).
Analysis of polymorphisms in genes associated with the FA/BRCA pathway in three patients with multiple primary malignant neoplasms
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Le Wang, Hao Wang, Ting Wang, Jinhui Liu, Wei Chen, Yamin Wang, Chao Chen, Hongli Zhu, Penggao Dai
String 10.5 software was used to analyze the signalling pathways of the genes containing the variations (Table 6). Genes containing the BPIP1 and FANCG variations in patient 1, FANCD2, BRCA2, and FANCM variations in patient 2, and FANCL and FANCA variations in patient 3 are involved the Fanconi anaemia pathway. The MLH3 and BRCA2 genes form a network through BRCA2, while the ATM, MSH, and BRCA1 genes and Fanconi anaemia pathway form a network through BRCA1. These genes are involved in the DNA mismatch repair system. MEN1, ATM and CEBPA variations in patient 3 are involved the pathway of transcriptional misregulation in cancer. Overall, all variations were detected in genes involved in the Fanconi anaemia pathway to form a complex network system (Figure 6).