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Biochemical Markers in Ophthalmology
Published in Ching-Yu Cheng, Tien Yin Wong, Ophthalmic Epidemiology, 2022
Abdus Samad Ansari, Pirro G. Hysi
Another early genetic risk factor identified through family-based linkage studies was located on the short arm of chromosome 10 in a single large multigeneration British family [36]. Subsequent fine-mapping analyses found that a missense mutation in the optineurin (OPTN) gene was the source of the linkage signal. This and other rare variants within the OPTN gene may be responsible for up to 17% of familial cases of glaucoma [37] and contribute a sizable number of POAG cases in the general population [38–40]. Unlike MYOC gene variants, the OPTN one almost invariably leads to low- and normal-pressure POAG cases [41, 42], highlighting the importance of both IOP and disc-related mechanisms underlying disease.
A History of Mental Retardation
Published in Merlin G. Butler, F. John Meaney, Genetics of Developmental Disabilities, 2019
Giovanni Neri, Francesco D. Tiziano
In spite of these intriguing theories, the exact pathophysiology of Down syndrome remains elusive. A great bulk of studies has been performed more recently in order to define the regions of chromosome 21 responsible for the single phenotypic characteristics and many animal models of the disease have been constructed (31–34). After these studies, especially based on mouse models and on the rare segmental human trisomies, it is now clear that the region around 21q22.3, syntenic to part of murine chromosome 16, is responsible for some of the characteristics of the syndrome, like craniofacial and limb morphology, duodenal stenosis, hypotonia, and joint hyperlaxity (32). The remaining human chromosome 21 is syntenic with part of murine chromosome 10 and 17.
Neurological and Mental Disorders
Published in Victor A. Bernstam, Pocket Guide to GENE LEVEL DIAGNOSTICS in Clinical Practice, 2019
RFLP analysis of malignant astrocytomas revealed LOH on all autosomes except chromosome 21, and the number of chromosomes with LOH correlated with tumor histopathology. A particularly frequent event, especially in GBM, was loss of broad regions of chromosome 10. Also frequent was LOH on chromosome 17p.
Controversies and Disparities in the Management of Age-Related Macular Degeneration
Published in Seminars in Ophthalmology, 2023
Aaron M. Fairbanks, Deeba Husain
AMD is a complex multifactorial disease with influences from both genetics and the environment. Age and smoking are the predominant risk factors, but the chances of developing the disease are increased for first-degree relatives of an affected individual, and twin studies have also demonstrated a substantial role for genetics in the disease.62,63 In 2005, the Y402H polymorphism in the CFH gene on chromosome 1 was found to be associated with an increased likelihood of developing AMD.64,65 Six years later, a rare variant in the CFH gene (R1210C) was identified and demonstrated strong penetrance and earlier onset of AMD.66 In 2006, single nucleotide polymorphisms in the ARMS2/HTRA1 (HtrA serine peptidase) genes on chromosome 10 were also found to confer an attributable risk of developing AMD, although a more recent and much larger study suggested that the ARMS2 variants exclusively increased the risk.67 In the following years, many other genes were associated with AMD, including those involved in the complement cascade (CFB, CFI, C2, C3, C9), angiogenesis (TGFBR1, VEGFA), extracellular collagen matrix (COL10A1, COL8A1), high-density lipoprotein cholesterol pathway (APOE, CETP, and LIPC), and immune regulation (TOLR3, PILRB).63,68–70 Together, these data indicate that AMD is a genetically complex disease involving multiple biochemical pathways and cellular mechanisms.
Importance of mannose-binding lectin2 polymorphism (rs1800450) in infections in children
Published in Biomarkers, 2022
Metin Uysalol, Suheyla Gumus, Raif Yildiz, Ezgi Pasli Uysalol, Sacide Pehlivan, Mustafa Pehlivan, Istemi Serin
Mannose-binding lectin (MBL) is a serine protease belonging to the collectin family and is believed to be an important factor in the inherited immune system. MBL binds to the surface of a wide range of microorganisms by its ability to recognise, function either directly as an opsonin or through activation of the complement system, thus increasing the phagocytosis of microorganisms by macrophages and neutrophils (Jacobson et al.2020). There are several known mutations in the MBL2 gene and promoter regions located on the long arm of chromosome 10, resulting in a large number of haplotypes. This genetic polymorphism is associated with different levels of MBL expression and activity (Best et al.2009, Jacobson et al.2020). Studies are showing that genotypes associated with low MBL levels may predispose to certain forms of infection or impaired immune response, particularly in neonates as well as adults (Best et al.2009, Jacobson et al.2020). Several studies on the association of MBL genetic polymorphism and/or MBL plasma levels with severe infections, sepsis, and septic shock have shown an increased risk of developing sepsis in patients with MBL deficiency (Eisen et al.2003, Best et al.2009). In our study, we aimed to reveal the distribution of different MBL genotypes in patients diagnosed with acute bronchiolitis and pneumonia.
Protein kinase inhibitors for the treatment of prostate cancer
Published in Expert Opinion on Pharmacotherapy, 2021
Vincent Chau, Ravi A. Madan, Jeanny B. Aragon-Ching
The phosphatidylinositol 3-kinase (PI3K) pathway plays a role in prostate carcinogenesis and castration resistance [64]. The PI3K are enzymes that are involved in the phosphorylation of membrane inositol lipids and facilitate signal transduction, eventually recruiting AKT/protein kinase B (PKB) kinases to the cell membrane for activation [65]. There are three classes of PI3K (class I, II, and III), each of which has unique functions within the cell [66]. Activated AKT then further triggers downstream signals involved in survival, proliferation, cell cycle progression, growth, migration, and angiogenesis [64]. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a negative regulator of AKT, and knockdown of PTEN increases tumor sphere formation and clonogenic and tumorigenic potential in laboratory studies [67]. Moreover, cross-talk exists between the PI3K/AKT pathway and the androgen receptor (AR) pathway such that inhibition of PI3K/AKT pathway upregulates the androgen receptor pathway and vice versa, thereby maintaining tumor cell survival [68]. The PI3K pathway is commonly activated in prostate cancer, with somatic alterations in 49% of mCRPC patients, including biallelic loss of PTEN, hotspot mutations, amplifications, activating fusions in PIK3CA, and activating mutations in AKT1[69].