Frequency of hereditary hemochromatosis gene mutations and their effects on iron overload among beta thalassemia patients of Chennai residents

<abstract> <p>Hereditary Hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism associated with <italic>HFE</italic> gene mutations, characterized by increased iron absorption and accumulation leading to multi-organ damage caused by iron overload toxicity. Beta thalassemia is caused by a mutation in the human beta globin gene. Imbalanced production of globin chain results in beta thalassemia, where the unpaired alpha chains precipitates in red cell precursors leading to ineffective erythropoiesis and reduced RBC survival. Both HH and beta thalassemia condition results in rapid accumulation of iron lead to iron overload in tissues and organs. The study aims to analyze the frequency of <italic>HFE</italic> variants among beta thalassemia cases and their effect on iron overload. The frequency of three <italic>HFE</italic> variants C282Y, H63D, S65C was analyzed by PCR RFLP method among Beta Thalassemia Trait (BTT) (n = 203), Beta Thalassemia Major (BTM) (n = 19) and age and sex-matched control samples (n = 200). The present study furnished allele frequency of H63D variant in BTT, BTM and controls 8.13, 15.8 and 6% respectively. Ten out of 33 heterozygous H63D variants exhibited iron overload with higher ferritin levels indicating <italic>HFE</italic> variant might aggravate the absorption of iron. The C282Y variant was present in heterozygous state in 1 case among beta thalassemia carriers. The C282Y variant was absent among BTM and control cases. S65C <italic>HFE</italic> variant was absent in the present study. Iron overload was completely absent in the control cases among all three <italic>HFE</italic> genotypes. Hence it is inferred from the present investigation, analysis of <italic>HFE</italic> genes and iron status will remarkably help to reason out the probable reason behind the iron status and support in proper management of beta thalassemia cases.</p> </abstract>

A truncation mutation in the L1CAM gene in a child with hydrocephalus

<abstract> <p>Hydrocephalus is a neurodevelopmental, X-linked recessive disorder caused by mutations in the <italic>L1CAM</italic> gene. The <italic>L1CAM</italic> gene encodes for L1CAM protein which is essential for the nervous system development including adhesion between neurons, Myelination, Synaptogenesis etc. Herein, the present study has reported mutations in L1 syndrome patient with Hydrocephalus and Adducted thumb. Genomic DNA was extracted from patients whole blood (n = 18). The 11 exons of the <italic>L1CAM</italic> gene were amplified using specific PCR primers. The sequenced data was analysed and the pathogenicity of the mutation was predicted using the various bioinformatics programs: PROVEAN, PolyPhen2, and MUpro. The results revealed that the proband described here had nonsense mutation G1120→T at position 1120 in exon 9 which is in extracellular immunoglobulin domain (Ig4) of the <italic>L1CAM</italic> gene. This nonsense mutation is found to be truncated with a deleterious effect on developing brain of the child, and this is the first report of this novel mutation in patient with X-linked Hydrocephalus in India.</p> </abstract>

Genetic variation in alcoholism and opioid addiction susceptibility and treatment: a pharmacogenomic approach

<abstract> <p>Alcohol and opioid abuse have pervasive and detrimental consequences from the individual to societal level. The extent of genetic contribution to alcoholism has been studied for decades, yielding speculative and often inconsistent results since the previous discovery of two pharmacokinetic variants strongly protective against alcoholism. The neurobiology of addiction involves innumerate genes with combinatorial and epistatic interactions, creating a difficult landscape for concrete conclusions. In contrast, pharmacogenomic variation in the treatment of alcoholism yields more immediate clinical utility, while also emphasizing pathways crucial to the progression of addiction. An improved understanding of genetic predisposition to alcohol abuse has inherent significance for opioid addiction and treatment, as the two drugs induce the same reward pathway. This review outlines current knowledge, treatments, and research regarding genetic predisposition to alcoholism, focusing on pharmacodynamic variation within the dopaminergic system and shared implications for opioid abuse. Multifaceted and highly polygenic, the phenotype of addiction seems to grow more complex as new research extends the scope of its impact on the brain, body, and progeny.</p> </abstract>

Cartilage type IIB procollagen NH2-propeptide, PIIBNP, inhibits angiogenesis

<abstract> <p>Cartilage tissue is avascular and resistant to tumor invasion, but the basis for these properties is still unclear. Here we report that the NH₂-propeptide of type IIB procollagen (PIIBNP), a product of collagen biosynthesis, is capable of inhibiting angiogenesis both <italic>in vitro</italic> and <italic>in vivo</italic>. PIIBNP inhibits tube formation in human umbilical vein cells (HUVEC), inhibits endogenous endothelial cell outgrowth in mouse aortic ring angiogenesis bioassay and is anti-angiogenic in the mouse cornea angiogenesis assay. As α_Vß₃ and α_Vß₅ integrins are expressed primarily in endothelial cells, cancer cells and osteoclasts, but not in normal chondrocytes and PIIBNP binds to cell surface integrin α_Vß₃ and αVß₅, we propose that natural occurring PIIBNP protects cartilage by targeting endothelial cells during chondrogenesis, thus inhibiting angiogenesis, and rendering the tissue avascular.</p> </abstract>