RESUMEN
Induced pluripotent stem cells (iPSCs) derived from diseased patients behave as a powerful tool for biomedical research and may provide a source for replacement therapies. In this study, we generated iPSCs from amniotic fluid cells of a fetus with Hb Bart's (γ4) disease (- -/- -). The established iPSCs showed pluripotency similar to that of human embryonic stem cells. They were able to differentiate into various somatic cell types and maintained normal karyotypes after long periods of culture in vitro. The patient-specific iPSCs offer a valuable model for advancing α-thalassemia (α-thal) research and early treatment of the affected fetuses.
Asunto(s)
Líquido Amniótico/citología , Hemoglobinas Anormales/genética , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/metabolismo , Biomarcadores , Diferenciación Celular , Reprogramación Celular , Homocigoto , Humanos , Inmunohistoquímica , Cariotipo , Fenotipo , Eliminación de Secuencia , Talasemia alfa/genéticaAsunto(s)
Hidrocefalia/genética , Deformidades Congénitas de las Extremidades/genética , Mutación Missense , Receptores de Interleucina/genética , Adulto , Secuencia de Aminoácidos , China , Secuencia Conservada , Análisis Mutacional de ADN , Femenino , Sangre Fetal/química , Muerte Fetal , Asesoramiento Genético , Pruebas Genéticas , Heterocigoto , Humanos , Hidrocefalia/complicaciones , Hidrocefalia/diagnóstico por imagen , Hidrocefalia/embriología , Deformidades Congénitas de las Extremidades/complicaciones , Deformidades Congénitas de las Extremidades/diagnóstico por imagen , Deformidades Congénitas de las Extremidades/embriología , Mutación Puntual , Embarazo , Receptores de Interleucina/química , Ultrasonografía Prenatal , Secuenciación del ExomaRESUMEN
We first report a novel ß chain variant, Hb Heze [ß144(HC1)LysâArg; HBB: c.434A>G], in a Chinese family. Heterozygous inheritance of the mutation results in a mild ß-thalassemia (ß-thal) phenotype, whereas compound heterozygosity of Hb Heze with ß0-thal appears as the cause of ß-thal intermedia (ß-TI) in our case.
Asunto(s)
Pueblo Asiatico/genética , Hemoglobinas Anormales/genética , Mutación , Globinas beta/genética , Talasemia beta/diagnóstico , Talasemia beta/genética , Alelos , Sustitución de Aminoácidos , China , Codón , Análisis Mutacional de ADN , Índices de Eritrocitos , Femenino , Genotipo , Humanos , Masculino , Linaje , Fenotipo , Talasemia beta/sangreAsunto(s)
Muestra de la Vellosidad Coriónica , Retardo del Crecimiento Fetal/genética , Pruebas Genéticas , Proteínas con Homeodominio LIM/genética , Mutación , Factores de Transcripción/genética , Regiones no Traducidas 3' , Aborto Eugénico , Adulto , Sustitución de Aminoácidos , China , Composición Familiar , Femenino , Retardo del Crecimiento Fetal/diagnóstico por imagen , Retardo del Crecimiento Fetal/metabolismo , Asesoramiento Genético , Heterocigoto , Humanos , Proteínas con Homeodominio LIM/química , Proteínas con Homeodominio LIM/metabolismo , Medida de Translucencia Nucal , Embarazo , Primer Trimestre del Embarazo , Factores de Transcripción/química , Factores de Transcripción/metabolismo , Secuenciación del ExomaRESUMEN
Hb Zurich-Albisrieden [HBA2: c.178G > C; α59(E8)GlyâArg (α2)] is a rare nondeletional α-thalassemia (α-thal) that results from a nucleotide substitution at codon 59 of the α2-globin gene. In this report, we present a fetus with cardiomegaly, enlarged placenta and increased middle cerebral artery-peak systolic velocity (MCA-PSV) at 25 weeks' gestation. Fetal blood sampling revealed the severe anemia [hemoglobin (Hb) level being 5.5 g/dL] and Hb H (ß4) disease-like hematological findings with Hb Bart's (γ4) level of 30.7%. Molecular analysis of the family found that the father was an Hb Zurich-Albisrieden carrier, the mother heterozygous for the - -SEA α0-thal deletion, and the fetus was a compound heterozygote for Hb Zurich-Albisrieden and the - -SEA α0-thal deletion. Therefore, this was a rare case of Hb Bart's hydrops fetalis associated with Hb Zurich Albisrieden.
Asunto(s)
Hemoglobinas Anormales/genética , Heterocigoto , Hidropesía Fetal/genética , Recolección de Muestras de Sangre , Femenino , Enfermedades Fetales/diagnóstico , Enfermedades Fetales/genética , Humanos , Hidropesía Fetal/diagnóstico , Masculino , Linaje , Mutación Puntual , Embarazo , Diagnóstico Prenatal , Eliminación de Secuencia , Globinas alfa/genética , Talasemia alfa/genéticaRESUMEN
Unstable hemoglobin (Hb) variants represent a rare etiology of congenital hemolytic anemia. Correct diagnosis can be a challenge due to the relative rarity or lack of awareness of this disorder. We report an 18-month-old girl, who presented with a long-standing hemolytic anemia. Her diagnosis of unstable Hb Perth [ß32(B14)LeuâPro, HBB: c.98T > C] had not been made until gene sequencing of the ß-globin gene was performed.
Asunto(s)
Anemia Hemolítica Congénita/genética , Mutación Missense , China , Femenino , Hemoglobinas Anormales/genética , Humanos , Lactante , Análisis de Secuencia de ADN , Globinas beta/genéticaRESUMEN
An elevated Hb A2 (α2δ2 level) is a diagnostic marker for heterozygous ß-thalassemia (ß-thal). Mutations in the δ-globin gene can cause decreased expression of Hb A2, compromising screening for heterozygous ß-thal. In this report, we describe a novel missense mutation of the δ-globin [Hb A2-Fengshun or δ121(GH4)GluâLys, HBD: c.364G > A] in a Chinese individual who had coinherited a heterozygous ß-thal with a normal Hb A2 level.
Asunto(s)
Hemoglobina A2/genética , Mutación Missense , Globinas delta/genética , Pueblo Asiatico/genética , Hemoglobina A2/análisis , Heterocigoto , Humanos , Talasemia beta/diagnóstico , Talasemia beta/genéticaRESUMEN
Nondeletional α-thalassemia (α-thal) is the result of point mutations in critical regions of the α-globin genes, affecting mRNA processing, mRNA translation, or α-globin stability. Hb Constant Spring (Hb CS, HBA2: c.427T > C) is the most common nondeletional α-thal that results from a nucleotide substitution at the termination codon of the α2-globin gene. Hb Quong Sze (Hb QS, HBA2: c.377T > C) is another nondeletional α-thal in South China with the missense mutation at codon 125 of the α2-globin gene making this hemoglobin (Hb) variant highly unstable. Although homozygosity for Hb CS (α(CS)α/α(CS)α) or Hb QS (α(QS)α/α(QS)α) has been reported, clinical pictures vary from severe hemolysis that developed early in life to only mild anemia, no clinical phenotypic data of compound heterozygosity for Hb CS/Hb QS (α(CS)α/α(QS)α) has been described. In this report we describe an adult case with such a compound heterozygosity who presented with a mild α-thal.
Asunto(s)
Hemoglobinas Anormales/genética , Mutación/genética , Talasemia alfa/genética , Adulto , Anemia/genética , Homocigoto , Humanos , FenotipoRESUMEN
ß-Thalassemia (ß-thal) is one of the most common inherited single gene disorders in the world. The aim of this study was to describe the gestational age at prenatal diagnosis (PND) for ß-thal in at-risk women in mainland China. All pregnant women at-risk for ß-thal and undergoing PND at a Mainland Chinese tertiary obstetric center between January 2005 and December 2014 were included. Information required for the survey was obtained from prenatal records and delivery charts. In total, 1307 women underwent PND for ß-thal. The mean gestational age for the procedure was 18.5 weeks. There were 384 (29.0%) women with fetal diagnosis in early trimester (<14 weeks), 715 (55.0%) in early second trimester (14-24 weeks), and 208 (16.0%) in late second trimester or beyond (>24 weeks). Although the proportion of patients undergoing early PND increased along with the time span, the mean n gestational age was not decreased significantly during the study period. The delay in PND deprived couples of the opportunity to make informed decisions early in pregnancy.
Asunto(s)
Diagnóstico Prenatal , Talasemia beta/diagnóstico , Adulto , China , Toma de Decisiones , Femenino , Edad Gestacional , Humanos , Embarazo , Trimestres del Embarazo , Encuestas y CuestionariosRESUMEN
Mutations that cause destabilization of the hemoglobin (Hb) tetramer are a rare cause of hemolytic anemia. In contrast to the hemolytic anemia caused by enzyme deficiencies, a dominant mode of inheritance characterizes the unstable Hbs. Hb Alesha [ß67(E11)ValâMet; HBB: c.202G>A] is caused by a G>A mutation at codon 67 of the ß-globin gene, resulting in a valine to methionine substitution at helix E11. This replacement disrupts the apolar bonds between valine and the heme group, producing an unstable Hb and severe hemolysis. We report this rare hemoglobinopathy in a Chinese girl with severe hemolytic anemia, splenomegaly and frequent requirement for red blood cell (RBC) transfusions.
Asunto(s)
Anemia Hemolítica/genética , Hemoglobinas Anormales/análisis , Globinas beta/genética , Sustitución de Aminoácidos , Anemia Hemolítica/complicaciones , Pueblo Asiatico , Preescolar , Transfusión de Eritrocitos , Femenino , Hemoglobinopatías/genética , Hemoglobinas Anormales/genética , Humanos , Mutación Puntual , Estabilidad Proteica , Esplenomegalia/etiologíaRESUMEN
The double heterozygosity for α and ß chain variants leads to the formation of abnormal heterodimer hybrids, which could render laboratory diagnostics in a routine setting difficult. The following is the first report of a double heterozygosity for Hb Q-Thailand [α74(EF3)AspâHis; HBA1: c.223G>C] with α+-thalassemia (α+-thal) and Hb J-Bangkok [ß56(D7)GlyâAsp; HBB: c.170G>A] found in a Chinese family. Both subjects were healthy with normal or borderline hematological parameters. Hemoglobin (Hb) analyses showed a novel variant, Hb Q-Thailand and Hb J-Bangkok. Family studies helped in the initial recognition and in making presumptive diagnoses, but definitive diagnoses of these cases with complex α and ß chain variants could only be obtained after DNA analysis.
Asunto(s)
Hemoglobina J/genética , Hemoglobinas Anormales/genética , Heterocigoto , Adulto , Pueblo Asiatico/genética , Diagnóstico Diferencial , Femenino , Hemoglobinopatías/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Núcleo Familiar , Linaje , Fenotipo , Globinas alfa/genética , Globinas beta/genéticaRESUMEN
The aim of the present study was to investigate the anti-proliferation and pro-apoptosis effect of Coix lachrymajobi L varma-yuan on acute T lymphoblast leukemia cell line Jurkat cells and its mechanism. Jurkat cells were treated with Coix lachrymajobi L varma-yuan of various concentrations (0, 0.4, 0.8, 1.6 mg/ml) for 24h. The inhibitory ratio was measured by Cell Counting Kit-8. The effects of Coix lachrymajobi L varma-yuan on apoptosis of Jurkat cells were determined by Hoechst 33258, PI and Annexin V-FITC/PI double staining. The mitochondrial membrane potential was analyzed by JC-1 staining. The results demonstrated that Coix lachrymajobi L varma-yuan inhibited the proliferation of Jurkat cells, and induced chromatin condensation and fragmentation (characteristic of apoptosis) and loss of mitochondrial membrane potential. In conclusion, Coix lachrymajobi L varma-yuan can inhibit the cell proliferation and induce the apoptosis of Jurkat cells. These effects relate to loss of mitochondrial membrane potential. These results suggest that Coix lachrymajobi L varma-yuan may be of value in treating lymphoma.
