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1.  The South Asian Genome 
PLoS ONE  2014;9(8):e102645.
The genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.
doi:10.1371/journal.pone.0102645
PMCID: PMC4130493  PMID: 25115870
2.  A Novel Albumin Gene Mutation (R222I) in Familial Dysalbuminemic Hyperthyroxinemia 
Context:
Familial dysalbuminemic hyperthyroxinemia, characterized by abnormal circulating albumin with increased T4 affinity, causes artefactual elevation of free T4 concentrations in euthyroid individuals.
Objective:
Four unrelated index cases with discordant thyroid function tests in different assay platforms were investigated.
Design and Results:
Laboratory biochemical assessment, radiolabeled T4 binding studies, and ALB sequencing were undertaken. 125I-T4 binding to both serum and albumin in affected individuals was markedly increased, comparable with known familial dysalbuminemic hyperthyroxinemia cases. Sequencing showed heterozygosity for a novel ALB mutation (arginine to isoleucine at codon 222, R222I) in all four cases and segregation of the genetic defect with abnormal biochemical phenotype in one family. Molecular modeling indicates that arginine 222 is located within a high-affinity T4 binding site in albumin, with substitution by isoleucine, which has a smaller side chain predicted to reduce steric hindrance, thereby facilitating T4 and rT3 binding. When tested in current immunoassays, serum free T4 values from R222I heterozygotes were more measurably abnormal in one-step vs two-step assay architectures. Total rT3 measurements were also abnormally elevated.
Conclusions:
A novel mutation (R222I) in the ALB gene mediates dominantly inherited dysalbuminemic hyperthyroxinemia. Susceptibility of current free T4 immunoassays to interference by this mutant albumin suggests likely future identification of individuals with this variant binding protein.
doi:10.1210/jc.2013-4077
PMCID: PMC4191552  PMID: 24646103
3.  Presence of hepcidin-25 in biological fluids: Bile, ascitic and pleural fluids 
AIM: To examine body fluids such as ascitic fluid (AF), saliva, bile and pleural effusions for the presence of hepcidin using a novel radioimmunoassay (RIA).
METHODS: Serum samples were collected from 25 healthy volunteers (mean age: 36 ± 11.9 years, 11 males, 14 females). In addition bile was obtained from 12 patients undergoing endoscopic retrograde cholangiopancreatography (mean age: 66.9 ± 16.7 years, M:F = 5:7). Saliva was collected from 17 healthy volunteers (mean age: 35 ± 9.9 years, M:F = 8:9). Pleural and AF were collected from 11 and 16 patients [(mean age: 72 ± 20.5 years, M:F = 7:4) and (mean age: 67.32 ± 15.2 years, M:F = 12:4)], respectively. All biological fluid samples (serum, exudative and transudative fluids) were tested for the presence of hepcidin-25 molecule using RIA.
RESULTS: Hepcidin-25 was detected in all biological fluids tested. The mean ± SD hepcidin-25 in serum was 15.68 ± 15.7 ng/mL, bile 7.37 ± 7.4 ng/mL, saliva 3.4 ± 2.8 ng/mL, exudative fluid 65.64 ± 96.82 ng/mL and transudative fluid 14.1 ± 17.8 ng/mL.
CONCLUSION: We provide clear evidence that hepcidin-25 is present in bile, saliva, pleural and ascitic fluids. Hepcidin is likely to play a role here in innate immunity.
doi:10.3748/wjg.v16.i17.2129
PMCID: PMC2864838  PMID: 20440853
Hepcidin; Hepcidin assay; Hepcidin in biological fluids; Hepcidin in ascitic fluid; Bile; Exudates; Antimicrobial peptides
4.  Prohepcidin Levels in Refractory Anaemia Caused by Lead Poisoning 
Recent research evidence suggests a central role for hepcidin in iron homeostasis. Hepcidin is a hormone synthesized in the liver. Hepcidin is also thought to play a vital role in the pathogenic mechanism of anaemia in patients with inflammation or chronic disease. A 38-year-old female who presented with recurrent abdominal pain was found to have raised urinary porphyrins and a blood lead level of 779 μg/l. Her haemoglobin level was 8.3 g/dl. Her MCV was normal. Serum ferritin, B12 and folate were normal. Her serum prohepcidin level was 2,489 ng/ml (normal <450 ng/ml). To our knowledge, this is the first report of raised prohepcidin levels in a patient with anaemia of chronic disease resulting from lead poisoning.
doi:10.1159/000118035
PMCID: PMC3075166  PMID: 21490838
Hepcidin; Prohepcidin; Lead poisoning; Porphyrins; Abdominal pain; Sideroblastic anaemia
7.  Acquired Fibrinopenia in Pregnancy 
British Medical Journal  1955;2(4934):287-290.
PMCID: PMC1980270  PMID: 14389753

Results 1-8 (8)