Efficient identification of somatic mutations in acute myeloid leukaemia using whole exome sequencing of fingernail derived DNA as germline control.

Recent advances in next-generation sequencing have made it possible to perform genome wide identification of somatic mutation in cancers. Most studies focus on identifying somatic mutations in the protein coding portion of the genome using whole exome sequencing (WES). Every human genome has around 4 million single nucleotide polymorphisms (SNPs).

Novel α-Globin Splice Site Mutation (HBA2: c.96-5C>A) in Combination with Three-Gene Deletion Hb H Disease.

The choice of acceptor splice site during exon-exon splicing by the spliceosome is determined by a variety of factors. We report here a family with a novel acceptor splice site variant within intron 1 of the α-globin gene that provides some in vivo insight into the rules governing RNA splicing in homo sapiens. A 2-year-old female with Hb H disease, was found to have not only three α-globin genes deleted (- -/-α) but also a HBA2: c.

Evaluation of an immunochromatographic strip test for alpha-thalassaemia screening.

Introduction: Hb H inclusion test (HbH-i) commonly used for α-thalassaemia screening is not standardised and is labour-intensive. This study evaluated a strip test based on immunochromatographic detection of Hb Bart's (ICT) for use as a routine screening test for α-thalassaemia screening in the clinical laboratory setting.

Methods: The performance characteristics of the ICT was determined by comparing the results of ICT and HbH-i on 67 patients, and the α-globin genotype on 47 of these patients who also had the molecular analysis.

Hb Feilding [β12(A9)Thr → Pro; HBB: c.37A>C]: a novel unstable β-globin chain variant.

We report here a patient heterozygous for a previously unreported β chain variant. A 72-year-old Caucasian female was found to have an abnormal hemoglobin (Hb) as an incidental finding following Hb A1C analysis. There was no family history of anemia or hemoglobinopathy.

Two missense mutations identified in venous thrombosis patients impair the inhibitory function of the protein Z dependent protease inhibitor.

Protein Z-dependent protease inhibitor (ZPI) is a plasma inhibitor of factor (F)Xa and FXIa. In an earlier study, five mutations were identified within the ZPI gene of venous thrombosis patients and healthy controls. Two of these were nonsense mutations and three were missense mutations in important regions of the protein.

A +8 (-->CT) mutation within the 5' untranslated region of beta-globin down-regulates the mRNA transcription.

The 5' untranslated region (5'UTR) of beta-globin has been well characterized and is often used as a model for eukaryotic transcription/translation, but there are still questions regarding the mechanism of translational control. Mutations affecting the Cap site at + 1 and at positions +10, +22, +33 and +40-43 have been described, and it is thought that the initiator element required for transcription stretches from -2 to +7 relative to the Cap site with a downstream element situated from +10 to +15. The influence on initiation or translation of sequences between +7 and +10 is unknown.

Mutations within the protein Z-dependent protease inhibitor gene are associated with venous thromboembolic disease: a new form of thrombophilia.

Protein Z-dependent protease inhibitor (ZPI) is a serpin that inhibits the activated coagulation factors X and XI. The precise physiological significance of ZPI in the control of haemostasis is unknown although a deficiency of ZPI may be predicted to alter this balance. The coding region of the ZPI gene was screened for mutations using denaturing high-performance liquid chromatography.

Calcium sensing receptor gene A986S polymorphism and responsiveness to calcium supplementation in postmenopausal women.

Recently several studies in adolescent girls or premenopausal women have implicated the calcium sensing receptor (CASR) gene A986S polymorphism in calcium and bone metabolism. However, the role of this genetic variant in postmenopausal women, specifically the development of osteoporosis, is unknown. This study reports the findings of a randomized, double-blind, placebo-controlled study of healthy postmenopausal women followed for 2 yr while taking placebo or supplementary calcium.

Potential thrombophilic mutations/polymorphisms in patients with no flow-limiting stenosis after myocardial infarction.

Background: Although inherited thrombophilias are more common in patients with venous thromboembolism, their influence on the development of myocardial infarction (MI) requires clarification.

Methods And Results: To determine whether there are increased frequencies of mutations/polymorphisms in 14 genes potentially causing thrombophilia in patients with no flow-limiting stenoses after MI compared with patients with > or =1 flow-limiting stenosis of >50%, we studied 395 patients (60 with no flow-limiting stenosis) who underwent angiography at approximately 1 month. The mutations/polymorphisms studied included Factor V Leiden, prothrombin variant G20210A, beta-fibrinogen 448 (G/A), endothelial protein C receptor (23-base pair insertion), methyl tetrahydrofolate reductase 677 (C/T), platelet glycoprotein IIIa PlA1/A2, plasminogen activator inhibitor-1 4G/5G, angiotensin II type 1 receptor (A/C), hemochromatosis gene 282 (G/A), nitric oxide synthase (NOS) (3 forms: eNOS, eNOS3, eNOS4), p22 phox of NADPH oxidase C242T, and angiotensin-converting enzyme insertion/deletion polymorphism.