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Genetic Disorders
Published in Jeremy R. Jass, Understanding Pathology, 2020
Genomic imprinting may be suspected on clinical grounds when an inherited disease occurs in both males and females but is transmitted only by parents of a particular gender. Genomic imprinting may also be suspected when a disease arises do novo and is associated with parental disomy (in which an individual has two identical chromosomes derived from the same parent). Interestingly, both scenarios have been observed in the case of the Beckwith-Wiedemann syndrome, an inherited disorder associated with organomegaly, hemihypertrophy, gigantism and a propensity to tumours of childhood, notably nephroblastoma or Wilms’ tumour. Underlying this syndrome is the phenomenon of imprinting of the insulin-like growth factor 2 (IGF2)gene in female germ cells. A paternal disomy involving the locus 11p15.5 leads to a double dose of IGF2. This in turn accounts for the organ enlargement. Conversely, mutations or cytogenetic abnormalities involving the 1 lpl5.5 locus are thought to block the process of imprinting in the female germline. Females and their offspring may therefore possess two functioning copies of IGF2 and so express a double dose of the growth factor (Tycko, 1997).
Perlman Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Loss-of-function germline homozygous or compound heterozygous mutations in the DIS3L2 represent one of the mechanisms that converge on Igf2 (insulin-like growth factor 2) upregulation, leading to overgrowth and/or Wilms tumor (Figure 94.1). Indeed, homozygous deletions of DIS3L2 exon 6 or exon 9, which cause the loss of both RNA binding and degradation activity, are frequently identified in patients with Perlman syndrome. Analysis of compound heterozygous DIS3L2 mutations (c.[367-2A > G];[1328T > A]) from a Japanese patient indicates that non-allelic homologous recombination (NAHR) between two LINE-1 (L1) elements represents an important disease mechanism [10]. As missense mutation (c.1328 T > A, p.Met443Lys) retains RNA binding in both the cold-shock domains and the S1 domain, and partial exonuclease functions remain in at least one allele, long-term survival is possible [11].
Section 10
Published in Padmanabhan Ramnarayan, MCQs in Paediatrics for the MRCPCH, Part 1, 2017
Growth hormone (GH) secretion occurs in a rhythmic fashion under the alternating influence of GHRH and somatostatin. This peaks in sleep. Insulin-like growth factor-2 (IGF-2) is a product of GH metabolism in the liver and is therefore not a direct regulator of GH levels in blood. Hypoglycaemia is a potent stimulus for secretion of GH, being the basis for an insulin tolerance test for testing GH stimulation.
Bioinformatic Identification of Hub Genes and Analysis of Prognostic Values in Colorectal Cancer
Published in Nutrition and Cancer, 2021
Xinyi Lei, Jing Jing, Miao Zhang, Bingsheng Guan, Zhiyong Dong, Cunchuan Wang
A comprehensive elucidation of CRC initiation, progression, and metastasis will be helpful for the early diagnosis and precise treatment of CRC patients. The last study has demonstrated the signaling pathway of insulin-like growth factor-2 (IGF-2), which has the significance in initiation, progression, prognosis, and treatment in CRC (4). Another new study has shown that circulating tumor DNA (ctDNA) is considered as a meaningful prognostic indicator in stage III CRC, post-chemotherapy ctDNA may reveal CRC patients at high risk of recurrence despite completing chemotherapy (5). The sequence study has shown that some special non-coding RNA, such as has_circ_0067163, has_circ_0140188, has_circ_0002632, and so on, are related to CRC (6). An in-depth understanding of CRC's molecular biology can be beneficial for the diagnosis and treatment of CRC.
Dysregulation of lncRNA-H19 in cardiometabolic diseases and the molecular mechanism involved : a systematic review
Published in Expert Review of Molecular Diagnostics, 2021
Ana Iris Hernández-Aguilar, Carlos Aldair Luciano-Villa, Vianet Argelia Tello-Flores, Fredy Omar Beltrán-Anaya, Ma Isabel Zubillaga-Guerrero, Eugenia Flores-Alfaro
In individuals with CAD, the presence of polymorphisms in the H19 gene has been associated with the risk and severity of this disease, including rs217727 and rs2067051. The T variant of rs217727 was associated with an increased risk of CAD. It has been hypothesized that this variant may interfere with the inhibitory effect of H19 on insulin-like growth factor 2 (IGF-2), resulting in increased IGF-2 levels and CAD susceptibility. However, future studies should be conducted to elucidate the molecular processes that explain this effect [40]. Several studies have shown that H19 overexpression influences the atherosclerosis process that leads to CAD and MI, and might increase the risk of ischemic stroke [41–46]. Thus, various researchers have proposed the measurement of the expression of H19 in blood as a novel prognostic biomarker for the risk of CAD. Recently, a study investigated the association between H19 levels, and rs217727 and rs4929984 polymorphisms in the H19 gene and CAD. They found an upregulated expression of H19 in the peripheral blood of CAD patients compared to healthy controls. In addition, rs4929984 was associated with susceptibility to CAD in Han Chinese women. The A-G haplotype and A-rs4929984 alleles correlated with female susceptibility to CAD. Furthermore, rs217727 and rs4929984 were associated with the clinicopathological parameters of CAD cases [47].
Incorporating molecular biomarkers into clinical practice for gastric cancer
Published in Expert Review of Anticancer Therapy, 2019
Shunsuke Nakamura, Mitsuro Kanda, Yasuhiro Kodera
Insulin-like growth factor 2 (IGF2) is mitogenic and antiapoptotic. IGF2 is an imprinted gene, expressed predominantly from the paternal allele, and its expression is controlled by CpG-rich regions (differentially methylated regions [DMRs]). Biallelic expression of IGF2 is a common epigenetic aberration in human cancers that increases the expression of genes involved in mitosis [60]. Tahara et al [60] . investigated IGF2 DMRs and the methylation of long interspersed nucleotide element (LINE1) in leukocyte DNA and their associations with patients’ clinical features. In patients with GC, hypomethylation of IGF2 DMRs and LINE1 is significantly associated with advanced age. Hypermethylation of IGF2 DMRs and LINE1 is significantly associated with undifferentiated histologic type, advanced stage, lymphatic invasion positive, venous invasion, lymph node metastasis, peritoneal dissemination, liver metastasis, and metastases to other sites.