Assuntos
Hematemese/etiologia , Lábio/irrigação sanguínea , Doenças Raras , Telangiectasia Hemorrágica Hereditária/diagnóstico , Adulto , Aberrações Cromossômicas , Diagnóstico Diferencial , Gastroscopia , Genes Dominantes/genética , Hematemese/genética , Humanos , Masculino , Telangiectasia Hemorrágica Hereditária/genéticaAssuntos
Cromossomos Humanos Par 6/genética , Mutação de Sentido Incorreto , Rim Policístico Autossômico Recessivo/genética , Receptores de Superfície Celular/genética , Consanguinidade , Varizes Esofágicas e Gástricas/genética , Éxons/genética , Feminino , Marcadores Genéticos/genética , Testes Genéticos , Genótipo , Hematemese/genética , Hepatomegalia/genética , Humanos , Lactente , Fenótipo , Rim Policístico Autossômico Recessivo/diagnóstico , Esplenomegalia/genética , TunísiaRESUMO
Factor VII is a vitamin K-dependent zymogen that plays a key role in the initiation of the extrinsic pathway. A severe factor VII deficiency was identified in a 45-year old male whose plasma factor VII antigen was less than 60 ng/ml and expressed 5.2% of normal factor VII activity. DNA sequence analysis of the patient's factor VII gene showed a thymidine to guanine transversion at nucleotide 10968 in exon VIII that results in a novel amino acid substitution of His348 to Gln. The patient was homozygous for this mutation, whereas some of his family members were heterozygous. Both wild type and mutant factor VII were transiently expressed in COS-1 cells. The level of secreted mutant factor VII antigen was only 11.0% of the level of wild type factor VII. In CHO cells stably transfected with the mutant factor VII, only 37.3% of the total labeled FVII was secreted into the conditioned media and the remainder was retained inside the cells. These data suggest this mutation leads to factor VII deficiency due to the impaired secretion of the molecule.
Assuntos
Sítios de Ligação/genética , Deficiência do Fator VII/genética , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Testes de Coagulação Sanguínea , Células CHO , Células COS , Cricetinae , DNA Complementar , Fator VII/biossíntese , Fator VII/química , Fator VII/genética , Deficiência do Fator VII/sangue , Saúde da Família , Expressão Gênica , Hematemese/genética , Hemorragia , Homozigoto , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação de Sentido Incorreto , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Alinhamento de Sequência , Análise de Sequência de DNA , Radioisótopos de Enxofre , TransfecçãoRESUMO
Deep vein thrombosis occurs in 30% of patients with essential thrombocythemia, but rarely at initial diagnosis. We report two pediatric patients with essential thrombocythemia revealed by atypical deep vein thrombosis. First, a 16-year-old girl presented Budd-Chiari syndrome revealed by a hemorrhagic shock. Clinical exam revealed isolated splenomegaly. A search for thrombophilia found a factor V Leiden homozygous mutation and a Jak2 mutation. Bone marrow biopsy confirmed the diagnosis of a myeloproliferative disorder. The second case, a 17-year-old girl, had a routine examination by her physician that revealed splenomegaly. Ultrasonography displayed thrombus in the splenic and portal vein. An isolated Jak2 mutation was found and a myeloproliferative disorder was confirmed by bone marrow biopsy. The diagnosis of myeloproliferative disorder was made in both patients presenting atypical venous thrombosis with a Jak2 mutation and confirmed by bone marrow biopsy. These initial presentations of myeloproliferative disorders are rare in childhood and possibly underdiagnosed.