RESUMO
Hb Tacoma [ß30(B12)ArgâSer] is a missense variant that is caused by either an AGG>AGT or AGG>AGC substitution at codon 30 of the HBB gene. Currently, the latter is classified as a rare cause of ß0-thalassemia (ß0-thal). We propose that HBB: c.93G>C has been incorrectly assigned as ß0-thal and discuss whether HBB: c.93G>T or HBB: c.93G>C should be classified as ß+-thal instead, or as ß-globin variants without thalassemic effect. We present several subjects who are heterozygous for Hb Tacoma, one with HBB: c.93G>T and two with HBB: c.93G>C, to support our conclusions.
Assuntos
Hemoglobinas Anormais , Talassemia beta , Hemoglobinas Anormais/genética , Humanos , Mutação de Sentido Incorreto , Globinas beta/genética , Talassemia beta/diagnóstico , Talassemia beta/genéticaRESUMO
Hb Q-Thailand [α74(EF3)AspâHis (α1); HBA1: c.223 G>C] is an abnormal hemoglobin (Hb), variant found mainly in China and Southeast Asian countries. The association of the αQ-Thailand allele with other globin gene disorders has important implications in diagnosis. Here, we report a hitherto undescribed condition of patients with a double heterozygosity for Hb Q-Thailand with α0-thalassemia (α0-thal) and in combination with ß0-thalassemia (ß0-thal) in a Chinese family. Our study will provide some clinical manifestations, laboratory diagnosis and genetic counseling for complex hemoglobinopathies.
Assuntos
Hemoglobinas Anormais/genética , Mutação , alfa-Globinas/genética , Talassemia alfa/diagnóstico , Talassemia alfa/genética , Talassemia beta/diagnóstico , Talassemia beta/genética , Adulto , Povo Asiático/genética , Criança , China , Análise Mutacional de DNA , Feminino , Estudos de Associação Genética , Hemoglobinopatias/diagnóstico , Hemoglobinopatias/genética , Heterozigoto , Humanos , Masculino , Fenótipo , Talassemia alfa/sangue , Talassemia beta/sangueRESUMO
We report the molecular and hematological feature of a Thai woman who had clinical diagnosis of ß-thalassemia intermedia (ß-TI). Hemoglobin (Hb) high performance liquid chromatography (HPLC) analysis identified Hb A (64.4%), Hb F (12.3%) and Hb A2/E (15.9%) with small peaks of Hb Bart's (γ4) and Hb H (ß4). She was initially diagnosed as EA Bart's disease, which occurs from combination of Hb H disease and Hb E (HBB: c.79G > A) trait. However, the Hb analysis using capillary electrophoresis (CE) demonstrated no Hb E, 68.5% Hb A, 15.5% Hb F and 16.0% Hb A2. DNA analysis showed a compound heterozygosity for (ß(+)) -31 (A > G) (HBB: c.-81A > G) and (ß(0)) codon 17 (A > T) (HBB: c.52A > T) mutations and deletional Hb H (- -(SEA)/-α(3.7)). Thus, she was finally diagnosed with a combination of Hb H disease and compound heterozygosity of ß(+)/ß(0)-thalassemia (ß(+)/ß(0)-thal). The ß-globin mutations could affect not only hematological parameters but also elevate the Hb A2 levels. These effects could not be ameliorated by the coinheritance of Hb H disease. Therefore, a better understanding of the effects of this combination on hematological analysis data will be useful for providing accurate diagnosis, genetic counseling, prevention and control programs of ß-thalassemia major (ß-TM).
Assuntos
Códon , Hemoglobina A2/genética , Hemoglobina A2/metabolismo , Heterozigoto , Mutação , alfa-Globinas/genética , Globinas beta/genética , Adolescente , Análise Mutacional de DNA , Índices de Eritrócitos , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Talassemia beta/sangue , Talassemia beta/diagnóstico , Talassemia beta/genéticaRESUMO
A novel ß(0)-thalassemia (ß-thal) frameshift mutation, HBB: c.209delG; p.Gly70Valfs*20, is described in a 21-year-old African American female with ß-thalassemia major (ß-TM) due to compound heterozygosity for the ß(0)-thal mutation HBB: c.92+2T>C [formerly known as IVS-I-2 (T>C)] and HBB: c.209delG. The combination of these mutations demonstrates a complete lack of ß-globin chain synthesis, evidenced by the proband having no Hb A present.