Inherited disorders

Wilson disease (WD), an inherited disorder affecting copper metabolism, is characterized by hepatic cirrhosis and neuronal degeneration, which result from toxic levels of copper that accumulate in the liver and brain, respectively. We reported previously that the  1.3-kb promoter of the WD gene contains four metal response elements (MREs). Among the four MREs, MREa plays the most important role in the transcriptional activation of the WD promoter.

11p research12 01-06-2013 52 2   Download

People everywhere expected the new millennium to bring surprises. But the particular shock and horror that rippled through the international viticulture community in 2000 was most unexpected. It had been found that sixteen of the most highly prized varieties of wine-making grapes were the products of mating between the classic Pinot and the classically undervalued Gouais grape. This blew the proverbial cork off the industry's bottle because the Gouais was considered such an inferior specimen that there were even attempts to ban its cultivation in France during the Middle Ages.

8p zingzing09 24-04-2013 55 2   Download

Human acid sphingomyelinase (haSMase, EC 3.1.4.12) catalyzes the lysosomal degradation ofsphingomyelin to ceramide and phosphorylcholine. An inherited haSMase deficiency leads toNiemann–Pick disease, a severe sphingo-lipid storage disorder. The enzyme was purified and cloned over 10 years ago. Since then, only a fewstructural properties of haSMase have been elucidated.

13p tumor12 20-04-2013 34 1   Download

Cockayne syndrome (CS) is a rare inherited human genetic disorder char-acterized by developmental abnormalities, UV sensitivity, and premature aging. The CS group B (CSB) protein belongs to the SNF2-family of DNA-dependent ATPases and is implicated in transcription elongation, transcription coupled repair, and base excision repair. It is a DNA stimula-ted ATPase and remodels chromatin in vitro. We demonstrate for the first time that full-length CSB positively cooperates in ATP hydrolysis as a function of protein concentration....

9p fptmusic 11-04-2013 40 2   Download

Cystinosis is a lysosomal storage disease caused by an accumulation of insoluble cystine in the lumen of the lysosome. CTNSencodes the lyso-somal cystine transporter, mutations in which manifest as a range of disorders and are the most common cause of inherited renal Fanconi syndrome. Cystinosin, theCTNSproduct, is highly conserved among mam-mals.

15p awards 06-04-2013 36 3   Download

The GM2-activator protein (GM2AP) is an essential cofactor for the degradation of ganglioside GM2 by lyso-somal b-hexosaminidase A. It mediates the interaction between the water-soluble exohydrolase and its membrane-bound substrate at the lipid–water interphase. Inherited defects in the gene encoding this glycoprotein result ina fatal neurological storage disorder, the AB variant of GM2-gangliosidosis. To elucidate the mode of action of this gly-coprotein cofactor, we synthesized the two photoaffinity labels [ 14 C]C3 -TPD-GM2 and [ 14 C]C7 -TPD-GM2. ...

14p dell39 03-04-2013 56 3   Download

Protein misfolding is recognized as an important pathophysiological cause of protein deficiency in many genetic disorders. Inherited mutations can disrupt native protein folding, thereby producing proteins with misfolded conformations.

10p media19 04-03-2013 22 1   Download

Hyperphenylalaninemia (Online Mendelian Inheritance in Mandatabase: 261600) is an autosomal recessive disorder mainly due to mutations in the gene for phenylalanine hydroxylase; the most severe form of hyperphenylal-aninemia is classic phenylketonuria. We sequenced the entire gene for phenylalanine hydroxylase in 51 unrelated hyperphenylalaninemia patients from Southern Italy.

12p viettel02 22-02-2013 36 3   Download

Fragile X mental retardation protein (FMRP) is an RNA binding protein necessary for correct spatiotemporal control of neuronal gene expression in humans. Lack of functional FMRP causes fragile X mental retardation, which is the most common inherited neurodevelopmental disorder in humans.

10p cosis54 05-01-2013 44 4   Download

Huntington’s disease (HD) is an inherited neurodegenerative disorder characterized by cortico-striatal dysfunction and loss of glutamate uptake. At 7 weeks of age, R6/2 mice, which model an aggressive form of juvenile HD, show a glutamate-uptake deficit in striatum that can be reversed by treatment with ceftriaxone, a b-lactam antibiotic that increases GLT1 expression. Only at advanced ages ( 11 weeks), however, do R6/2 mice show an actual loss of striatal GLT1. Here, we tested whether ceftriaxone can reverse the decline in GLT1 expression that occurs in older R6/2s.

5p toshiba23 18-11-2011 51 3   Download

Abstract Hemochromatosis, the most common form of iron overload disease, is an inherited disorder that causes the body to absorb and store too much iron. The extra iron builds up in organs and damages them. Without treatment, the disease can cause these organs to fail. Tóm tắt Bệnh thặng dư sắt mô là một biến loạn di truyền làm cho cơ thể hấp thụ quá nhiều sắt hơn mức cần thiết. Nếu không được điều trị, lượng sắt tích tụ cao trong cơ thể có thể làm tổn hại những cơ quan thiết yếu và những khớp của cơ...

11p thiuyen111 11-04-2011 117 5   Download

Factor XI Deficiency: Treatment The treatment of FXI deficiency is based on the infusion of FFP at doses of 15–20 mL/kg to maintain trough levels ranging from 10 to 20%. Because FXI has a half-life of 40–70 h, the replacement therapy can be given on alternate days. The use of antifibrinolytic drugs is beneficial to control bleeds, with the exception of hematuria or bleeds in the bladder. The development of a FXI inhibitor was observed in 10% of severely FXI-deficient patients who received replacement therapy.

5p thanhongan 07-12-2010 86 4   Download

Harrison's Internal Medicine Chapter 110. Coagulation Disorders Coagulation Disorders: Introduction Deficiencies of coagulation factors have been recognized for centuries. Patients with genetic deficiencies of plasma coagulation factors exhibit lifelong recurrent bleeding episodes into joints, muscles, and closed spaces, either spontaneously or following an injury. The most common inherited factor deficiencies are the hemophilias, X-linked diseases caused by deficiency of Factor (F) VIII (hemophilia A) or Factor IX (FIX, hemophilia B).

5p thanhongan 07-12-2010 75 3   Download

von Willebrand Disease vWD is the most common inherited bleeding disorder. Estimates from laboratory data suggest a prevalence of approximately 1%, but data based on symptomatic individuals suggest that it is closer to 0.1% of the population. vWF serves two roles: (1) as the major adhesion molecule that tethers the platelet to the exposed subendothelium; and (2) as the binding protein for FVIII, resulting in significant prolongation of the FVIII half-life in circulation.

5p thanhongan 07-12-2010 62 2   Download

Thrombotic Thrombocytopenic Purpura TTP and HUS were previously considered overlap syndromes. However, in the past few years the pathophysiology of inherited and idiopathic TTP has become better understood and clearly differs from HUS. TTP was first described in 1924 by Eli Moschcowitz and characterized by a pentad of findings that include microangiopathic hemolytic anemia, thrombocytopenia, renal failure, neurologic findings, and fever. The full-blown syndrome is less commonly seen now, probably due to earlier diagnosis.

5p thanhongan 07-12-2010 76 2   Download

Thrombocytopenia Thrombocytopenia results from one or more of three processes: (1) decreased bone marrow production; (2) sequestration, usually in an enlarged spleen; and/or (3) increased platelet destruction. Disorders of production may be either inherited or acquired. In evaluating a patient with thrombocytopenia, a key step is to review the peripheral blood smear and to first rule out "pseudothrombocytopenia," particularly in a patient without an apparent cause for the thrombocytopenia. Pseudothrombocytopenia (Fig.

5p thanhongan 07-12-2010 67 2   Download

Approach to the Patient: Thrombocytopenia The history and physical examination, results of the CBC, and review of the peripheral blood smear are all critical components in the initial evaluation of the thrombocytopenic patients (Fig. 109-2). The overall health of the patient and whether he/she is receiving drug treatment will influence the differential diagnosis. A healthy young adult with thrombocytopenia will have a much more limited differential diagnosis than an ill hospitalized patient who is receiving multiple medications.

5p thanhongan 07-12-2010 79 2   Download

Hemoglobin E HbE (i.e., α2β226Glu - Lys) is extremely common in Cambodia, Thailand, and Vietnam. The gene has become far more prevalent in the United States as a result of immigration of Asian persons, especially in California, where HbE is the most common variant detected. HbE is mildly unstable but not enough to affect RBC life span significantly. The high frequency of the HbE gene may be a result of the thalassemia phenotype associated with its inheritance. Heterozygotes resemble individuals with mild β-thalassemia trait.

5p thanhongan 07-12-2010 90 3   Download

Severity is highly variable. Known modulating factors are those that ameliorate the burden of unpaired α-globin inclusions. Alleles associated with milder synthetic defects and co-inheritance of α-thalassemia trait reduce clinical severity by reducing accumulation of excess α globin. HbF persists to various degrees in β-thalassemias. γ-Globin gene chains can substitute for βchains, generating more hemoglobin and reducing the burden of α-globin inclusions. The terms β-thalassemia major and β-thalassemia intermedia are used to reflect the clinical heterogeneity.

5p thanhongan 07-12-2010 75 3   Download

Harrison's Internal Medicine Chapter 99. Disorders of Hemoglobin Disorders of Hemoglobin: Introduction Hemoglobin is critical for normal oxygen delivery to tissues; it is also present in erythrocytes in such high concentrations that it can alter red cell shape, deformability, and viscosity. Hemoglobinopathies are disorders affecting the structure, function, or production of hemoglobin. These conditions are usually inherited and range in severity from asymptomatic laboratory abnormalities to death in utero.

5p thanhongan 07-12-2010 87 9   Download