RESUMEN
We have identified a variant on the ß-globin gene in a Chinese female. Sequencing of the HBB gene revealed a PheâLeu substitution at codon 42[ß42(CD1) PheâLeu, HBB:c.129T > A] which has been named Hb Suqian for where the proband was born.
Asunto(s)
Hemoglobinas Anormales , Globinas beta , Femenino , Humanos , Globinas beta/genética , Codón , Pueblos del Este de Asia , Hemoglobinas Anormales/genéticaRESUMEN
We report a novel mutation on the ß-globin gene in a 68-year-old woman of Sicilian origin living in Alessandria, Italy. This mutation produces a hemoglobin (Hb) variant of Hb A that was detected by the capillary electrophoresis (CE) method during measurement of Hb A1c. The variant Hb did not separate from Hb A using different high performance liquid chromatography (HPLC) instruments. Direct DNA sequencing revealed a G>T transversion at codon 37 and subsequent substitution of a tryptophan residue for a leucine residue. The new Hb variant was named Hb Alessandria [ß37(C3)TrpâLeu; HBB: c.113G>T]. The p50 value was slightly decreased while the stability test at 37 °C in isopropyl alcohol and the main erythrocyte parameters were normal. Overall, the patient appeared clinically normal.
Asunto(s)
Hemoglobinas Anormales , Globinas beta , Femenino , Humanos , Anciano , Globinas beta/genética , Hemoglobinas Anormales/genética , Leucina/genética , Oxígeno , Electroforesis Capilar , Mutación , Cromatografía Líquida de Alta PresiónRESUMEN
We report a new hemoglobin (Hb) variant that we have named Hb Wanjiang (HBB: c.255_264delinsTTTTTCTCAG). We identified this variant in a Chinese man by the next-generation sequencing (NGS) method. The father of the proband also carried the same variant. This variant results from a 10 bp deletion at codons 84-87 of the ß-globin chain, replaced with 10 nucleotides coming from the δ-globin gene at the same position, leading to the substitution of two amino acids in the peptide chain with no change in the ß-globin chain length. The heterozygotes had a normal hematological feature with no abnormal Hb variant detectable on capillary electrophoresis (CE) and high performance liquid chromatography (HPLC). The combination of Hb Wanjiang and ß-thalassemia (ß-thal) was not found to aggravate anemia.
Asunto(s)
Hemoglobinas Anormales , Globinas delta , Sustitución de Aminoácidos , Aminoácidos , Codón , Hemoglobinas Anormales/genética , Humanos , Masculino , Nucleótidos , Globinas beta/química , Globinas beta/genética , Globinas delta/genéticaRESUMEN
A previously unknown hemoglobin (Hb) variant was detected during measurement of glycosylated Hb (Hb A1c) after the introduction of a new high performance liquid chromatography (HPLC) apparatus. Subsequent DNA sequencing revealed a heterozygous single nucleotide substitution at codon 79 (C>A) on the ß-globin gene changing an amino acid [ß79(EF3)AspâGlu; HBB: c.240C>A]. The new Hb variant was named Hb Kalundborg after the place of origin of the proband. Heterozygosity for this mutation appears to have no clinical significance in itself except for a possibly slightly lower oxygen affinity. However, it interferes with Hb A1c measurement by HPLC, causing a falsely high Hb A1c concentration when using the G11 apparatus with clinical implications possibly to follow.
Asunto(s)
Hemoglobinopatías , Hemoglobinas Anormales , Aminoácidos , Cromatografía Líquida de Alta Presión/métodos , Codón , Hemoglobina Glucada/análisis , Hemoglobinopatías/diagnóstico , Hemoglobinopatías/genética , Hemoglobinas Anormales/análisis , Humanos , Mutación , Nucleótidos , Oxígeno , Globinas beta/químicaRESUMEN
We report a de novo frameshift mutation in exon 3 of the ß-globin gene that leads to a ß-thalassemia (ß-thal) intermedia (ß-TI) phenotype in a 6-year-old Chinese boy. This novel mutation with deletion of the last nucleotide (-T) at codon 130 results in a ß-globin chain that is extended to 156 amino acid residues. This study highlights the importance of considering dominantly inherited ß-thal in the investigation of anemia, even in patients with ethnic backgrounds not usually associated with ß-thal and hematologically normal parents.
Asunto(s)
Globinas beta , Talasemia beta , Humanos , Globinas beta/genética , Globinas beta/química , Talasemia beta/diagnóstico , Talasemia beta/genética , Nucleótidos , Exones , Codón , MutaciónRESUMEN
We report a novel ß chain hemoglobin (Hb) variant found in a Chinese family. A high level of Hb F was observed on capillary electrophoresis (CE). However, high performance liquid chromatography (HPLC) showed a high level of Hb A2. DNA sequencing revealed a single base substitution (T>G) at codon 96 of exon 2 of the ß-globin gene. This alters the normally encoded leucine to arginine [ß96(FG3)LeuâArg; HBB: c.290T>G] that we propose to name Hb Laibin for the region of origin of the proband. The pedigree study showed that it was inherited from his mother.
Asunto(s)
Hemoglobinas Anormales , Arginina/genética , China , Codón , Hemoglobinas Anormales/genética , Humanos , Leucina/genética , Mutación , Globinas beta/genéticaRESUMEN
We report a novel hemoglobin (Hb) variant found in a Spanish individual from Santa Cruz de Tenerife, the Canary Islands in Spain. The proband was a 39-year-old male. High performance liquid chromatography (HPLC) displayed an unknown peak (19.3%) at a retention time of 1.3 min. eluting before Hb A0. Capillary zone electrophoresis (CZE) showed an abnormal peak (20.0%) in zone 12. Direct DNA sequencing of the α-globin genes revealed heterozygosity for a nonsense mutation at codon 139 (AAA>TAA), causing a lysine to stop codon substitution [α139(HC1)LysâStop; HBA1: c.418A>T]. We decided to name the variant Hb Nivaria (Tenerife) for the place of birth and residence of the proband.
Asunto(s)
Hemoglobinas , Lisina , Masculino , Humanos , Adulto , Hemoglobina Glucada , Cromatografía Líquida de Alta Presión , Electroforesis CapilarRESUMEN
Homozygous or compound heterozygous mutations of the ß-globin gene lead to ß-thalassemia (ß-thal) major (ß-TM) or ß-thal intermedia (ß-TI), whereas heterozygotes usually show microcytosis with negligible or no hemolysis. Certain missense mutations in exon 3, however, produce unstable globins causing a dominant ß-thal phenotype or hemolytic anemia in heterozygotes. Here we report a mutation in exon 3 of the ß-globin gene, which results in an unstable globin (Hb Dieppe) [ß127(H5)GlnâArg; HBB: c.383A>G] with a dominant ß-thal phenotype in two generations of a Chinese family. Physicians should be alerted to this mechanism of ß-thal considering its relative rarity.
Asunto(s)
Talasemia beta , Exones , Humanos , Mutación , Fenotipo , Globinas beta/genética , Talasemia beta/diagnóstico , Talasemia beta/genéticaRESUMEN
Here we report a novel α chain hemoglobin (Hb) variant found in a 74-year-old Chinese male. We accidentally discovered this Hb variant during the measurement of Hb A1c by a capillary electrophoresis (CE) method (Hb A1c program, CapillaryS3 TERA). However, Hb analysis with the Hb program of CapillaryS3 TERA and the VARIANT II™ ß-Thalassemia Short Program showed no indication of the Hb variant. Sanger sequencing revealed a new missense mutation on the HBA1 gene [HBA1: c.225C>G, codon 74 (GAC>GAG), AspâGlu]. We named it Hb Jishui after the birthplace of the proband.
Asunto(s)
Hemoglobinas Anormales , Anciano , Codón , Hemoglobina Glucada/genética , Hemoglobinas Anormales/genética , Humanos , Masculino , Mutación , Globinas alfa/genéticaRESUMEN
We have identified a new α chain hemoglobin (Hb) variant in a Chinese subject. Sequencing of the α-globin gene revealed a mutation in exon 1 at nucleotide 55, which results in the replacement of a glycine by cysteine at codon 18 [α18(A16)GlyâCys, HBA2: c.55G>T] that we have named Hb Jiujiang for the region of origin of the proband.
Asunto(s)
Cisteína , Hemoglobinas Anormales , Codón , Glicina/genética , Hemoglobina A2/genética , Hemoglobinas Anormales/genética , Humanos , Globinas alfa/genéticaRESUMEN
We here describe a novel hemoglobin (Hb) variant, Hb Liaobu [α107(G14)ValâLeu, HBA2: c.322G>C], in a Chinese family. The structurally abnormal α chain variant could not be detected using capillary electrophoresis (CE) and was subsequently characterized by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS), and further confirmed by reversed phase high performance liquid chromatography (HPLC). Sanger sequencing revealed a novel base mutation on the α2-globin gene and RNA analysis by reverse transcription polymerase chain reaction (RT-PCR) showed the presence of an abnormal HBA transcript. The isopropanol stability test indicated the stable state of this structural Hb variant. In conclusion, a new Hb variant, Hb Liaobu, was discovered and characterized. It was proven to be a nonpathogenic variant. Our study resolved the confusion in the clinical diagnosis of individuals with this novel Hb variant in this family.
Asunto(s)
Hemoglobinas Anormales , Electroforesis Capilar , Hemoglobinas Anormales/análisis , Hemoglobinas Anormales/genética , Humanos , Rayos Láser , Espectrometría de Masas , Mutación , Globinas alfa/análisis , Globinas alfa/genéticaRESUMEN
We report a novel mutation on the ß-globin gene in a female of the Chinese population. This mutation produces a ß-globin variant that can be detected by the capillary electrophoresis (CE) method, but coelutes with Hb A2 by high performance liquid chromatography (HPLC). DNA sequencing showed a mutation of codon 46 and it was named Hb Cenxi [ß46(CD5)GlyâArg (GGG>CGG), HBB: c.139G>C] for the city of birth of the proband. She presented normal hematological parameters.
Asunto(s)
Hemoglobinas Anormales , Electroforesis Capilar , Femenino , Hemoglobinas Anormales/análisis , Hemoglobinas Anormales/genética , Humanos , Mutación , Análisis de Secuencia de ADN , Globinas beta/análisis , Globinas beta/genéticaRESUMEN
We report a novel variant found in a female from Guilin municipality in the Guangxi Zhuang Autonomous Region of the People's Republic of China. This variant can be readily detected by both cation exchange high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Sanger sequencing revealed a novel mutation on the ß-globin gene [ß65(E9)LysâGlu (AAG>GAG); HBB: c.196A>G]. We named this novel hemoglobin (Hb) variant Hb Guangxi for the place of origin of the proband.
Asunto(s)
Hemoglobinas Anormales , Globinas beta , China , Cromatografía Líquida de Alta Presión , Electroforesis Capilar , Femenino , Hemoglobinas Anormales/genética , Humanos , Mutación , Globinas beta/genéticaRESUMEN
We here report a new hemoglobin (Hb) variant found in a Chinese woman. The presence of the Hb variant can be easily recognized by HbA1c procedures based on ion exchange high performance liquid chromatography (HPLC) or capillary electrophoresis (CE) techniques. DNA sequencing revealed a new point mutation (HBA2: c.49A>C) at codon 16, resulting in an amino acid substitution from lysine to glutamine. Moreover, the Hb variant affected Hb A1c determination by VARIANT II Turbo 2.0 and D100. We named the new Hb variant Hb Heilongjiang for the birthplace of the proband.
Asunto(s)
Hemoglobina A/genética , Globinas alfa/genética , Sustitución de Aminoácidos , Pueblo Asiatico/genética , Cromatografía Líquida de Alta Presión , Electroforesis Capilar , Femenino , Hemoglobinas Anormales/genética , Humanos , Persona de Mediana Edad , Mutación Puntual , Análisis de Secuencia de ADNRESUMEN
We report the case of a 61-year-old Canadian male of Maltese descent investigated for unexplained polycythemia. Decreased p50 suggested the presence of a high oxygen affinity hemoglobin (Hb) variant. Molecular genetic testing demonstrated that he carries a novel missense mutation (HBB: c.258T>G), resulting in a PheâLeu substitution at position 85 of the ß chain. The novel Hb variant has been designated Hb Kennisis in recognition of where the proband resides. Two other missense mutations have been reported at this position [Hb Bryn Mawr or Hb Buenos Aires, ß85(F1)PheâSer (HBB: c.257T>C); Hb Grantham, ß85(F1)PheâCys; (HBB: c.257T>G)], both of which have increased oxygen affinity.
Asunto(s)
Hemoglobinas Anormales/genética , Mutación Missense , Oxígeno/metabolismo , Policitemia/genética , Globinas beta/genética , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Hemoglobinas Anormales/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Policitemia/sangre , Policitemia/diagnóstico , Policitemia/fisiopatología , Unión Proteica , Globinas beta/metabolismoRESUMEN
Patients with unstable hemoglobin (Hb), caused by a qualitative abnormality in α- and ß-globin genes, are often asymptomatic or mildly symptomatic. It is often difficult to diagnose unstable Hb patients with only mild hemolysis or low oxygen saturation. We herein report a case of a family with an unstable Hb, specifically, Hb Sydney (HBB: c.203T>C), an abnormal ß-globin chain. A 5-year-old boy was referred to our hospital for low percutaneous oxygen saturation (SpO2) in the setting of bronchitis. During hospitalization, low SpO2 persisted despite the improvement in respiratory distress symptoms. As he had mild hemolysis and splenomegaly, his disease was diagnosed to carry Hb Sydney based on gene analysis. His mother and brother also carried Hb Sydney. In this case, bronchial asthma had been treated, but unstable Hb was not assessed. Low SpO2 may be tolerated and overlooked in cases of asthma and it took time to diagnose this patient. The present case suggests that unstable Hb should be considered in patients with bronchial asthma and prolonged low SpO2.
Asunto(s)
Anemia Hemolítica/genética , Asma/genética , Hemoglobinas Anormales/genética , Mutación , Globinas beta/genética , Talasemia beta/genética , Adulto , Anemia Hemolítica/diagnóstico , Anemia Hemolítica/etnología , Pueblo Asiatico , Asma/diagnóstico , Asma/etnología , Secuencia de Bases , Preescolar , Familia , Femenino , Expresión Génica , Humanos , Masculino , Linaje , Análisis de Secuencia de ADN , Globinas beta/deficiencia , Talasemia beta/diagnóstico , Talasemia beta/etnologíaRESUMEN
Here we report a 67-year-old Chinese male carrying an unstable novel hemoglobin (Hb) variant in compound heterozygosity with the - -SEA (Southeast Asian) α-thalassemia (α-thal) deletion. Hemoglobin analysis by capillary electrophoresis (CE) revealed a rapid degradation feature of the variant. Sanger sequencing of the Hb gene revealed a novel homozygous mutation in exon 2 of the α1-globin gene [α52(E1)SerâCys (TCT>TGT); HBA1: c.158C>G]. We named this novel variant Hb Dongguan for the place of origin of the proband. Additionally, gap-polymerase chain reaction (gap-PCR) indicated the presence of the heterozygous - -SEA α-thal deletion.
Asunto(s)
Hemoglobinas Anormales/genética , Heterocigoto , Globinas alfa/genética , Talasemia alfa/genética , Anciano , Pueblo Asiatico , Electroforesis Capilar , Homocigoto , Humanos , Masculino , Mutación , Estabilidad Proteica , Eliminación de SecuenciaRESUMEN
We report the molecular and hematological identifications of a Hb A2 variant [coinheritance of Hb A2-Melbourne (HBD: c.130G>A) and Hb E (HBB: c.79G>A)] found for the first time in the Lao People's Democratic Republic (PDR). The subject was a 29-year-old pregnant Laotian woman who was a foreign worker in Thailand and was diagnosed with thalassemia and hemoglobinopathies. Capillary electrophoresis (CE) demonstrated 1.6% of Hb A2, with a minor unknown peak at the initial Z1 zone (1.7%). Identification of abnormal hemoglobin (Hb) using direct DNA sequencing showed a genetic defect causing a δ-globin gene missense mutation at codon 43 (GAG>AAG) causing a glutamic acid to lysine substitution corresponding to Hb A2-Melbourne. The origin of Hb A2-Melbourne in Lao PDR may be similar to a case found in Thailand with the [+ - - - - + +] haplotype. We developed a method that could clearly detect Hb A2-Melbourne and Hb A2-Lampang (HBD: c.142G>A) mutations in a single tube using high resolution melt (HRM) analysis. The HRM analysis is a more effective method for rapid detection than conventional polymerase chain reaction (PCR), as there is no need for a post-PCR step, and no exposure to ethidium bromide. This new method would be a useful addition for the first investigation of a suspected Hb A2 variant in the routine molecular setting.
Asunto(s)
Alelos , Genotipo , Hemoglobina E/genética , Hemoglobinas Anormales/genética , Patrón de Herencia , Mutación , Biomarcadores , Análisis Mutacional de ADN , Índices de Eritrocitos , Femenino , Hemoglobinopatías/diagnóstico , Hemoglobinopatías/genética , Humanos , Laos , Reacción en Cadena de la Polimerasa , EmbarazoRESUMEN
We report a novel ß-globin chain variant, Hb Shenzhen [ß90(F6)GluâAla, HBB: c.272A>C], in a 52-year-old Chinese individual. The hemoglobin (Hb) variant takes the position of the Hb D zone using capillary electrophoresis. Sanger sequencing revealed a novel base mutation on the ß-globin gene, HBB: c.272A>C, that resulted in a transition of glutamic acid to alanine at exon 2 of the ß-globin gene. We named this novel variant Hb Shenzhen for the geographic origin of this proband.
Asunto(s)
Hemoglobinas Anormales/genética , Mutación Missense , Globinas beta/genética , Pueblo Asiatico , Electroforesis Capilar , Humanos , Persona de Mediana Edad , Mutación Puntual , Análisis de Secuencia de ADNRESUMEN
We report here a novel α1-globin chain variant, Hb Hubei [α114(GH2)ProâHis, HBA1: c.344C>A], in a Chinese individual. The proband, a 28-year-old Chinese female, was discovered following routine Hb A1c analysis using cation exchange high performance liquid chromatography (HPLC). Sanger sequencing revealed a novel missense mutation, HBA1: c.344C>A (CCC>CAC), in exon 2 of the α1-globin gene. The mutation caused a transition of proline to histidine at position α114(GH2) on the α1-globin chain. This new variant was named Hb Hubei after the geographic origin of the proband.