ACTN1 mutations lead to a benign form of platelet macrocytosis not always associated with thrombocytopenia
| Autor: | Caterina Marconi, Marco Seri, Roberta Bottega, Annalisa Pastore, Michela Faleschini, Federica Melazzini, Elena Cigalini, Tania Giangregorio, Alessandro Pecci, Tommaso Pippucci, Patrizia Noris, Ugo Ramenghi, Anna Savoia, Timo Siitonen |
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| Přispěvatelé: | Faleschini, Michela, Melazzini, Federica, Marconi, Caterina, Giangregorio, Tania, Pippucci, Tommaso, Cigalini, Elena, Pecci, Alessandro, Bottega, Roberta, Ramenghi, Ugo, Siitonen, Timo, Seri, Marco, Pastore, Annalisa, Savoia, Anna, Noris, Patrizia |
| Rok vydání: | 2018 |
| Předmět: |
Adult
Blood Platelets Male 0301 basic medicine medicine.medical_specialty Erythrocytes Platelet Aggregation DNA Mutational Analysis Autosomal dominant macrothrombocytopenia Mutation Missense Erythrocytes Abnormal thrombocytopenia Macrocytosis Disease 03 medical and health sciences 0302 clinical medicine ACTN1-related thrombocytopenia ACTN1 gene macrocytosis mutations Actinin Aged Blood Cell Count Child Female Hematologic Diseases Humans Middle Aged Pedigree Thrombocytopenia Mutation Internal medicine medicine OMIM : Online Mendelian Inheritance in Man Missense mutation Gene macrocytosi Hematology business.industry medicine.disease 030104 developmental biology Immunology Cohort Abnormal Missense mutation business 030215 immunology |
| Zdroj: | British Journal of Haematology. 183:276-288 |
| ISSN: | 0007-1048 |
| Popis: | The inherited thrombocytopenias (IT) are a heterogeneous group of diseases resulting from mutations in more than 30 different genes. Among them, ACTN1-related thrombocytopenia (ACTN1-RT; Online Mendelian Inheritance in Man: 615193) is one of the most recently identified forms. It has been described as a mild autosomal dominant macrothrombocytopenia caused by mutations in ACTN1, a gene encoding for one of the two non-muscle isoforms of alpha-actinin. We recently identified seven new unrelated families with ACTN1-RT caused by different mutations. Two of them are novel missense variants (p.Trp128Cys and p.Pro233Leu), whose pathogenic role has been confirmed by in vitro studies. Together with the 10 families we have previously described, our cohort of ACTN1-RT now consists of 49 individuals carrying ACTN1 mutations. This is the largest case series ever collected and enabled a critical evaluation of the clinical aspects of the disease. We concluded that ACTN1-RT is the fourth most frequent form of IT worldwide and it is characterized by platelet macrocytosis in all affected subjects and mild thrombocytopenia in less than 80% of cases. The risk of bleeding, either spontaneous or upon haemostatic challenge, is negligible and there are no other associated defects, either congenital or acquired. Therefore, ACTN1-RT is a benign form of IT, whose diagnosis provides affected individuals and their families with a good prognosis. |
| Databáze: | OpenAIRE |
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