Rare Variants in GP1BB underlie Autosomal Dominant Macrothrombocytopenia; Findings of Large Unique Bleeding and Platelet Disorders Cohort
نویسندگان
چکیده
منابع مشابه
Proteins linked to autosomal dominant and autosomal recessive disorders harbor characteristic rare missense mutation distribution patterns.
The role of rare missense variants in disease causation remains difficult to interpret. We explore whether the clustering pattern of rare missense variants (MAF < 0.01) in a protein is associated with mode of inheritance. Mutations in genes associated with autosomal dominant (AD) conditions are known to result in either loss or gain of function, whereas mutations in genes associated with autoso...
متن کاملRare bleeding disorders.
During the haemostatic response, the formation of a primary platelet plug limits bleeding and provides a surface for clotting factors to assemble and become activated. The initial platelet plug is stabilized by fibrin monomers, covalently cross-linked by FXIII, forming a platelets-fibrin thrombus. Defects in platelets as well as inherited deficiencies of coagulation factors including fibrinogen...
متن کاملAutosomal dominant macrothrombocytopenia in Italy is most frequently a type of heterozygous Bernard-Soulier syndrome.
A form of autosomal dominant macrothrombocytopenia is characterized by mild or no clinical symptoms, normal platelet function, and normal megakaryocyte count. Because this condition has so far received little attention, patients are subject to misdiagnosis and inappropriate therapy. To identify the molecular basis of this disease, 12 Italian families were studied by linkage analysis and mutatio...
متن کاملMutations in tropomyosin 4 underlie a rare form of human macrothrombocytopenia
Platelets are anuclear cells that are essential for blood clotting. They are produced by large polyploid precursor cells called megakaryocytes. Previous genome-wide association studies in nearly 70,000 individuals indicated that single nucleotide variants (SNVs) in the gene encoding the actin cytoskeletal regulator tropomyosin 4 (TPM4) exert an effect on the count and volume of platelets. Plate...
متن کاملPlatelet hyperreactivity explains the bleeding abnormality and macrothrombocytopenia in a murine model of sitosterolemia.
Sitosterolemia is a rare, autosomal recessive disease caused by mutations in the adenosine triphosphate-binding cassette transporter genes ABCG5 or ABCG8 that result in accumulation of xenosterols in the body. Clinical manifestations include tendon xanthomas, premature coronary artery disease, hemolytic anemia, macrothrombocytopenia, and bleeding. Although the effect of sterol accumulation on t...
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ژورنال
عنوان ژورنال: Blood
سال: 2016
ISSN: 0006-4971,1528-0020
DOI: 10.1182/blood.v128.22.1359.1359