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We report a novel β 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 β-globin gene. This alters the normally encoded leucine to arginine [β96(FG3)Leu→Arg; 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. [ABSTRACT FROM AUTHOR]

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 β-globin gene changing an amino acid [β79(EF3)Asp→Glu; 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. [ABSTRACT FROM AUTHOR]

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)Lys→Stop; HBA1: c.418A>T]. We decided to name the variant Hb Nivaria (Tenerife) for the place of birth and residence of the proband. [ABSTRACT FROM AUTHOR]

We here describe a novel hemoglobin (Hb) variant, Hb Liaobu [α107(G14)Val→Leu, 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. [ABSTRACT FROM AUTHOR]

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 β-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 β-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 β-thalassemia (β-thal) was not found to aggravate anemia. [ABSTRACT FROM AUTHOR]

Homozygous or compound heterozygous mutations of the β-globin gene lead to β-thalassemia (β-thal) major (β-TM) or β-thal intermedia (β-TI), whereas heterozygotes usually show microcytosis with negligible or no hemolysis. Certain missense mutations in exon 3, however, produce unstable globins causing a dominant β-thal phenotype or hemolytic anemia in heterozygotes. Here we report a mutation in exon 3 of the β-globin gene, which results in an unstable globin (Hb Dieppe) [β127(H5)Gln→Arg; HBB: c.383A>G] with a dominant β-thal phenotype in two generations of a Chinese family. Physicians should be alerted to this mechanism of β-thal considering its relative rarity. [ABSTRACT FROM AUTHOR]

We report a novel mutation on the β-globin gene in a female of the Chinese population. This mutation produces a β-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 [β46(CD5)Gly→Arg (GGG>CGG), HBB: c.139G>C] for the city of birth of the proband. She presented normal hematological parameters. [ABSTRACT FROM AUTHOR]

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™ β-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), Asp→Glu]. We named it Hb Jishui after the birthplace of the proband. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We have identified a variant on the β-globin gene in a Chinese female. Sequencing of the HBB gene revealed a Phe→Leu substitution at codon 42[β42(CD1) Phe→Leu, HBB:c.129T > A] which has been named Hb Suqian for where the proband was born. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 Phe→Leu substitution at position 85 of the β 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, β85(F1)Phe→Ser (HBB: c.257T>C); Hb Grantham, β85(F1)Phe→Cys; (HBB: c.257T>G)], both of which have increased oxygen affinity. [ABSTRACT FROM AUTHOR]

Patients with unstable hemoglobin (Hb), caused by a qualitative abnormality in α- and β-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 β-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. [ABSTRACT FROM AUTHOR]

A small group of hemoglobin (Hb) variants result from 'in-frame' deletion/insertion (del/ins). We describe a new variant of this group (Hb Choisy), found on the α1 gene, which is the exact counterpart of a previously published deletional variant, Hb J-Biskra [codons 51-58 (or codons 52-59) (-24 bp) (-TCTGCCCAGGTTAAGGGCCACGGC); HBA1: c.157_180del (or HBA2)]. In Hb J-Biskra, the sequence Ser-Ala-Gln-Val-Lys-Gly-His-Gly located from positions α52(E1) to α59(E8) is deleted, while in Hb Choisy the same sequence (Ser-Ala-Gln-Val-Lys-Gly-His-Gly) is inserted at position α52(E1). The variant carrying the insertion appears to be less damaging than the one with the deletion. A possible explanation could be that the additional sequence is located in the C to E interhelical region, and is less disturbing to the general structure of the globin chain. This insertion/deletion (ins/del) is likely favored by the repetition, at an interval of 16 nucleotides, of an eight nucleotide sequence. Comparison of variants of this group, found in the HbVar database, shows that structural modifications resulting from insertions are frequently less damaging than that caused by deletions. [ABSTRACT FROM AUTHOR]

Brazilian Quilombolas are communities composed of African-derived populations that have their territories guaranteed by the Brazilian Constitution. The present study investigated the hemoglobin (Hb) variants among these population groups. This study was conducted in a total of 2843 individuals of Brazilian Quilombola communities of the Bahia, Pará, and Piauí states. All the participants had their Hb profiles evaluated. The Hb S (HBB: c.20A>T) variant was described in all the studied localities. However, the individuals in Bahia State had the highest frequency of the Hb C (HBB: c.19G>A) variant; individuals from Piauí State had a higher frequency of the Hb D-Punjab (HBB: c.364G>C) variant compared to the other states, and individuals from Pará State only carried the Hb S variant. The present study revealed a specific distribution of Hb variants that could represent different waves of African influence in these Brazilian populations. [ABSTRACT FROM AUTHOR]

We describe a novel C>T substitution at codon 53 of theHBBgene (HBB: c.161C>T). The proband was a transfusion-dependent β-thalassemia major (β-TM) patient. DNA was extracted and subsequently, DNA sequencing was done to detect the mutations on theHBBgene. Capillary zone electrophoresis (CZE) revealed the presence of an unknown peak. She inherited this mutation from her grandmother through her mother. This mutation exists inciswith the common β0mutation IVS-I-5 (G>C) (HBB: c.92+5G>C). The proband is homozygous forHBB: c.92+5G>C and needs monthly transfusions. On the other hand, her grandmother, mother and sister all possess this novel mutationciswith the heterozygousHBB: c.92+5G>C. They are carriers not thalassemic. This mutation produces the substitution β53(D4)Ala→Val;HBB: c.161C>T, a new structural hemoglobin (Hb) variant. As this variant was identified in a Bengali family from Paschim Midnapore district of West Bengal, India, it has been designated as Hb Midnapore. This variant has now been reported to the HbVar database. [ABSTRACT FROM AUTHOR]

We present a case of a novel pathogenic variant, Hb Kalavasos [α91(FG3)Leu→His (α2);HBA2: c.275T > A; p.Leu92His (NM_000517.4)]; this codon was previously numbered 91 on the α2-globin gene that was discovered following routine Hb A1ctesting on a 65-year-old female of Cypriot origin. The band, seen by high performance liquid chromatography (HPLC) but not capillary zone electrophoresis (CZE), was confirmed as a hitherto undescribed a chain variant, that we have named Hb Kalavasos for the Cypriot village of family origin of the proband. [ABSTRACT FROM AUTHOR]

A 59-year-old Italian woman came to our center for revaluation of a previous diagnosis of polycythemia vera. The patient presented with a lifelong history of polycythemia, no increase in white blood cells (WBCs) and platelets, and a negative bone marrow biopsy. Analysis of hemoglobin (Hb) fractions showed an abnormal fast moving Hb component. We aimed to determine if this variant was the cause of polycythemia in this patient. A complete blood count (CBC) was performed by an automated cell counter and Hb fractions were determined by high performance liquid chromatography (HPLC). Standard stability tests and oxygen affinity evaluation were also performed. Genomic DNA was extracted from peripheral blood leukocytes using the phenol chloroform method and the entire β-globin gene was analyzed by direct sequencing. At the hematological level, no anemia or hemolysis was observed but an abnormal Hb fraction was detected using cation exchange HPLC. Molecular analysis of the β-globin gene showed heterozygosity for an AAG > ACG substitution at codon 144, resulting in a Lys→Thr amino acid replacement. We demonstrated that this is a new Hb variant with increased oxygen affinity. Its altered physiology is caused by the reduction of 2,3-diphosphoglycerate (2,3-DPG) effects, due to an amino acid substitution in the central pocket near the C-terminal of the β chain. We called this new variant Hb San Cataldo for the native city of proband. [ABSTRACT FROM AUTHOR]

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 β-globin gene [β65(E9)Lys→Glu (AAG>GAG); HBB: c.196A>G]. We named this novel hemoglobin (Hb) variant Hb Guangxi for the place of origin of the proband. [ABSTRACT FROM AUTHOR]

We report a novel β-globin chain variant, Hb Shenzhen [β90(F6)Glu→Ala, 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 β-globin gene, HBB: c.272A>C, that resulted in a transition of glutamic acid to alanine at exon 2 of the β-globin gene. We named this novel variant Hb Shenzhen for the geographic origin of this proband. [ABSTRACT FROM AUTHOR]

We report here a novel α1-globin chain variant, Hb Hubei [α114(GH2)Pro→His, 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. [ABSTRACT FROM AUTHOR]

We identified two novel δ-globin gene mutations in two families during routine thalassemia screening. One missense mutation at codon 73 on the δ-globin gene [δ73(E17)Asp→Val, HBD: c.221A>T] which results in a Hb A2 variant homologous to the β-globin gene variant called Hb Mobile [β73(E17)Asp→Val, HBB: c.221A>T] and we have named this variant Hb A2-Henan. The other is a nonsense mutation [δ7(A4)Glu→Stop, HBD: c.22G>T] which gives rise to a stop codon (TAG) at codon 7, resulting in δ0-thalassemia (δ0-thal). The Hb A2 in one individual with homozygous HBD: c.22G>T was absent. [ABSTRACT FROM AUTHOR]

We report two families, members of which are carriers of a hemoglobin (Hb) variant previously described as Hb Nouakchott [α114(GH2)Pro→Leu; HBA1: c.344C>T; p.Pro115Leu]. In the first family of Dutch origin, the proband, a 32-year-old male and his 65-year-old father, were both carriers of Hb Nouakchott. Of the second family we tested, only the proband, a 56-year-old Dutch female was a Hb Nouakchott carrier. Hematological analyses of these cases showed the anomaly behaves as a silent Hb variant without clinical consequences. The Hb variant remained unnoticed using high performance liquid chromatography (HPLC), while an additional peak was detected by capillary electrophoresis (CE). These independent findings of Hb Nouakchott indicate that this Hb variant might not be very rare, but simply remains under diagnosed depending on the Hb separation technique used. [ABSTRACT FROM AUTHOR]

Glycosylated hemoglobin (Hb A1C) is a crucial indicator for the long-term control and the diagnosis of diabetes. However, the presence of hemoglobin (Hb) variants may affect the measured value of Hb A1C and result in an abnormal graph trend and inconsistency between the clinical blood sugar test and Hb A1C values. In this study, laboratory data of 41,267 patients with diabetes were collected. The Hb A1C levels and the graph results were examined. We identified 74 cases containing abnormal Hb A1C graph trends. The conducted blood cell counts and capillary Hb electrophoresis were used to analyze Hb variants. We also determined gene variation for the Hb variants by a sequence approach. Fifteen different types of Hb variants were identified in this study. Among these, we found a novel variant in which the α1 subunit of Hb showed an insertion of 24 nucleotides (nts) between the 56th and 57th residues. We named this novel variant Hb Kaohsiung Veterans General Hospital (Hb KSVGH) ( HBA1: p.Lys57_Gly58insSerHisGlySerAlaGlnValLys). [ABSTRACT FROM AUTHOR]

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)Gly→Cys, HBA2: c.55G>T] that we have named Hb Jiujiang for the region of origin of the proband. [ABSTRACT FROM AUTHOR]

We report a novelHBB: c.114G>C mutation in a Chinese family. This mutation resulted in a β37(C3)Trp→Cys amino acid substitution and was synonymous with Hb Kent, a hemoglobin (Hb) variant that was reported exclusively in patients of European descent. Though Hb Kent has a normal oxygen affinity and molecular stability, it has a characteristic dual variant appearance on cellulose acetate electrophoresis (CAE) and high performance liquid chromatography (HPLC) caused by the posttranslational modification of cysteine. We also report the phenotypic expression of this variant when coinherited with the Southeast Asian (– –SEA) double α-globin gene deletion. [ABSTRACT FROM AUTHOR]

We report a clinical update of the hemoglobin (Hb) variant [β27(B9)Ala→Gly;HBB: c.83C>G], named Hb Siirt, that was previously described as a silent variant in a 23-year-old Kurdish female. The patient was also a carrier of the codon 5 (–CT) (HBB: c.17_18delCT) frameshift mutation and of the αααanti 3.7triplication. Her initial moderate β-thalassemia intermedia (β-TI) phenotype worsened with time, causing the patient to become a transfusion-dependent subject at the age of ∼40 years. Subsequent molecular characterization of both parents revealed that the Hb Siirt variant was inherited by the mother, while the other two globin alterations (HBB: c.17_18delCT and αααanti 3.7triplication) were genetically transmitted by the father. The latter remained a carrier of a mild β-TI phenotype throughout his life, at least until the age of 65 years. We hypothesize that the worsened clinical conditions in the daughter were due to the additional, maternally inherited Hb Siirt variant. However, protein 3D conformational analysis did not seem to reveal substantial overall structural changes. Among the other three described variants [Hb Volga (HBB: c.83C>A), Hb Knossos (HBB: c.82 G>T), Hb Grange-Blanche (HBB: c.83C>T] that are due to nucleotide substitutions at codon 27 of the β-globin gene; only Hb Knossos causes a β+-thalassemia (β+-thal) phenotype. [ABSTRACT FROM AUTHOR]

We first report a novel β chain variant, Hb Heze [β144(HC1)Lys→Arg;HBB: c.434A>G], in a Chinese family. Heterozygous inheritance of the mutation results in a mild β-thalassemia (β-thal) phenotype, whereas compound heterozygosity of Hb Heze with β0-thal appears as the cause of β-thal intermedia (β-TI) in our case. [ABSTRACT FROM AUTHOR]

Hb Memphis [α23(B4)Glu→Gln; HBA2: c.70G > C (or HBA1)] is a stable hemoglobin (Hb) variant caused by a substitution of glutamine for glutamic acid at residue 23 of the α2- or α1-globin chain. Heterozygous Hb Memphis has no known clinical or hematological effect, and all prior reports have resulted from observations in persons of African descent with sickle cell disease and an unusually mild clinical course. Family studies suggest that Hb Memphis may modulate sickling. Only brief characterizations of Hb Memphis trait in the absence of Hb S are present in the current literature. We report isolated Hb Memphis trait in Turkish individuals in whom the initial laboratory incorrectly identified the α variant as Q-Thailand [α74(EF3)Asp→His; HBA1: c.223G > C]. In one case, a heterozygous −3.7 kb α gene deletion was also present, which increased the variant Hb level to a percentage similar to that of the more common Hb Q-Thailand, which may have led to the misidentification. Herein, we discuss the characterization and comparison of these variants and underscore the necessity of confirming characterization by more than one method prior to assigning Hb variant identification. [ABSTRACT FROM AUTHOR]

Hb Constant Spring [Hb CS, α142, Term→Gln, TAA>CAA (α2)] is a nondeletional form of α-thalassemia (α-thal) that is most prevalent in Southern Chinese and Southeast Asian populations. We previously found that Hb CS trait could efficiently be screened using Sebia Capillarys2. In this study, we report that Hb CS heterozygotes combined with β-thal could not be detected by the Sebia Capillarys2 method due to the very small amount of Hb CS. [ABSTRACT FROM AUTHOR]

We report a new hemoglobin (Hb) variant [β86(F2)Ala→Val; HBB:c.260C>T] that we have named Hb Izmir. We have identified Hb Izmir in a Turkish woman by ion exchange high performance liquid chromatography (HPLC) during a premarital screening program in the Aegean region of Turkey. The mother and sister of the proband also carried the same variant. Using direct sequencing, we have characterized this variant as resulting from a G CC>G TC replacement at codon 86 of the β-globin chain, corresponding to an Ala→Val amino acid substitution. In the heterozygote, the level of Hb Izmir ranged from 41.38 to 45.6%. All heterozygotes had a Hb A2 level of less than 3.5%. Total blood count values were normal and there were no other clinical findings. Although its clinical significance is thus far unclear, Hb Izmir may be important in hemoglobinopathy screening programs. [ABSTRACT FROM AUTHOR]

All Hb Hammersmith [β42(CD1)Phe→Ser, TTT>TCT] patients reported so far have been female, suggesting that this condition may occur as a negative, fatal intrauterine selection against males. In this case report, we describe a male case of Hb Hammersmith. A 6-month-old male patient, born from ovum donation, presented with hemolytic anemia and cyanosis. Hemoglobin (Hb) electrophoresis revealed decreased Hb A (54.0%%) and Hb A2 (0.3%%) and markedly increased Hb F (45.7%%) levels. Direct sequencing revealed a missense mutation in the HBB gene, c.128T>C (p.Phe42Ser), which is known as Hb Hammersmith. This mutation was not identified in any of this patient's family members. This is the first case of Hb Hammersmith in a male patient, and this study demonstrates that Hb Hammersmith is likely a non fatal condition for males during the intrauterine period. [ABSTRACT FROM AUTHOR]

We describe a Chinese woman who was assumed to be heterozygous for both Hb E [β26(B8)Glu→Lys] and α0-thalassemia (α0-thal) by a high performance liquid chromatography (HPLC) method, but was later also shown to be a Hb New York [β113(G15)Val→Glu] heterozygote by the Sebia CapillaryS2 system. This study suggested that a single test is never sufficient to allow the correct diagnosis of an abnormal hemoglobin (Hb). We also emphasize the importance of a correct diagnosis of interactions between α- and β-thalassemias. [ABSTRACT FROM AUTHOR]

We have identified a new αα chain hemoglobin (Hb) variant in a Chinese family. Sequencing of the amplified αα2-globin gene revealed a 9 nucleotide (nt) deletion (--C GAG TAT GG) at codons 22--25, which results in a predicted αα-globin chain that is missing amino acid residues 23--25 (Glu-Tyr-Gly) and the formation of Hb Zhanjiang. [ABSTRACT FROM AUTHOR]

Hb Constant Spring [Hb CS; α142, Term→Gln (TAA>CAA in α2)] is a nondeletional α-thalassemia (α-thal) defect difficult to detect on conventional electrophoresis because of its small amount in heterozygotes. We have found that individuals with an Hb CS trait could efficiently be detected using the Sebia capillarys 2 system. In the present study, we have confirmed this method in a cohort of 23,842 individuals from Guangdong Province (South China). Hb CS was detected in 71 (0.3%) of the cases. The levels of Hb CS in heterozygotes ranged from 0.1-1.0% with an average of 0.6%. We propose the reported 0.3% as a realistic figure for the prevalence of Hb CS in South China. [ABSTRACT FROM AUTHOR]

A new β hemoglobin (Hb) variant, Hb Cambridge-MA [β144(HC1)β146(HC3)Lys-Tyr-His→0 (AAG>TAG) (HGVS: HBB c.433 A>T] is described. The variant was characterized by high performance liquid chromatography (HPLC), alkaline, acid, globin chain and capillary electrophoresis, isoelectric focusing (IEF), heat and isopropanol stability, p50 analyses, intact globin mass spectrometry (MS) and DNA sequencing. The new variant shows high oxygen (O2) affinity and is associated with mild polycythemia. [ABSTRACT FROM AUTHOR]

Routine hemoglobin (Hb) analyses identified a new β-globin variant in a family from East Timor. The red cell indices were within normal limits for all affected family members. The variant is due to a missense mutation at amino acid codon 80 (AAC>CAC) which results in the substitution of histidine for asparagine. [ABSTRACT FROM AUTHOR]

We describe a heterozygosity for a new missense mutation on the α1-globin gene of an 18-year-old woman of Portuguese ancestry with severe hypochromic anemia and iron deficiency. Hemoglobin (Hb) analysis by high performance liquid chromatography (HPLC) found a prominent peak constituting about 12% of total Hb. Sequencing of the globin genes of the index patient found the mutation α14(A12)Trp→Leu (α1), HBA1:c.44G

Hb Constant Spring [Hb CS; α142, Term→Gln ( TAA> CAA in α2)] is the most prevalent nondeletional α-thalassemia (α-thal) anomaly in southern China. In conjunction with α0-thal, it can cause severe Hb H (β4) disease. The present study was done to evaluate the efficiency of two diagnostic methods in detecting Hb CS. Automated high performance liquid chromatography (HPLC) and Sebia Capillarys 2, a capillary electrophoresis method, were applied to blood samples from 21 individuals with Hb CS trait. Of the 21 cases, all (100%) were detected by capillary electrophoresis, whereas only 16 (76.2%) were detected by HPLC. We concluded that the Sebia Capillarys 2 is the preferred method for Hb CS screening. [ABSTRACT FROM AUTHOR]

Here we describe Hb F-Avellino [Gγ41(C7)Phe → Leu;HBG2: c.124 T > C], a new hemoglobin (Hb) variant observed in a healthy newborn. The proband’s hemolysate was found to be mildly unstable by the isopropanol test. The occurrence of the variant was assessed by both chromatographic and electrophoretic methods. DNA sequencing analysis of theGγ gene showed a T to C transition at codon 41 (TTC > CTC) corresponding to the Phe → Leu substitution. Normal functional properties have been hypothesized. [ABSTRACT FROM PUBLISHER]

Routine antenatal hemoglobinopathy screening detected a new α chain variant that eluted with Hb A2 on cation exchange high performance liquid chromatography (HPLC) in a lady of Sri Lankan origin who had normal hematological indices. The mutation was identified by electrospray ionization mass spectrometry (ESI-MS) as α46(CE4)Phe→Val, inferring that the variant was due to a single base change at codon 46 (TTC>GTC) of the α1- or α2-globin genes. [ABSTRACT FROM AUTHOR]

We present here five new hemoglobin (Hb) variants which have been identified during routine Hb analysis before their genotypic characterization. Four of these result from a classical missense mutation: Hb Canuts [α85(F6)Asp→His (α1)], Hb Ambroise Pare [α117(GH5)Phe→Ile (α2)], Hb Beaujolais [β84(EF8)Thr→Asn] and HbA2-North Africa [δ59(E3)Lys→Met]. The last one, Hb Monplaisir [β147 (Tyr-Lys-Leu-Ala-Phe-Phe-Leu-Leu-Ser-Asn-Phe-Tyr-158-COOH)], results from a frameshift mutation at the stop codon of the β-globin gene which leads to a modified C-terminal sequence in the β-globin chain. None of these variants seem to have a particular clinical expression in the heterozygous state. The circumstances of the discovery of these five new Hb variants emphasize the fact that an association of techniques is necessary for a complete screening of Hb variants during routine Hb analysis. Globin chain separation by reversed phase liquid chromatography (RP-LC) appears to be the most relevant method. [ABSTRACT FROM AUTHOR]

When analyzed by routine cation exchange high performance liquid chromatography (HPLC), the Hb A1c peak of a Caucasian diabetic patient from Yorkshire, UK, appeared to be an incompletely resolved doublet. One component (5.5%) eluted at the normal time for Hb A1c, whereas the other component (6.6%) eluted slightly later. The HPLC trace was otherwise normal. Analysis of the diabetic patient's blood and a tryptic digest thereof by electrospray ionization mass spectrometry (ESI-MS) identified the Hb Belleville trait. To relate Hb A1c determined by HPLC to α and β chain glycation determined by ESI-MS, several normal blood samples (5-14% Hb A1c) were analyzed by both techniques. The Hb A1c levels derived from the α and β chain glycation levels of the diabetic patient (12.9 and 12.4%, respectively) agreed with the sum of the two peaks (12.1%) in the HPLC trace. Similarly, Hb Belleville was detected and identified in another Caucasian, also from Yorkshire, with normal Hb A1c. [ABSTRACT FROM AUTHOR]

We report the case of a 56-year-old Caucasian woman in whom hemoglobinopathy screening was triggered following an aberrant Hb A1canalysis. Preliminary diagnosis of the hemoglobin (Hb) variant was obtained through cation exchange high performance liquid chromatography (HPLC) and gel electrophoresis. DNA analysis confirmed the presence of Hb J-Amiens [β17(A14)Lys→Asn;HBB: c.[54G > C or 54G > T)]. However, an unbalanced ratio between wild type and mutant signal after direct sequencing and a lower than expected percentage of this Hb variant led to the suggestion of a mosaic expression. Furthermore, different methods [capillary zone electrophoresis (CZE), cation exchange HPLC and boronate affinity] were tested to study the possible interference of this variant with Hb A1cmeasurements. These investigations showed a clinically relevant difference between the methods tested. Hb A1canalysis may lead to the discovery of new Hb variants or mosaicism for previously described Hb variants. This may have genetic consequences for the offspring of carriers and brings about the question of partner testing. [ABSTRACT FROM AUTHOR]

We report a new hemoglobin (Hb) variant on theHBA2gene, Hb Zara [α91(FG3)Leu→Ile (α2);HBA2: c.274C > A], which was found in a Caucasian man from Croatia. It was observed by routine cation exchange chromatography as an abnormal 21.8% fraction overlapping Hb A2, and associated with normal hematology. It was slightly unstable by the standard isopropanol precipitation test. DNA analysis revealed theCTT > ATT mutation at codon 91 on an α2 gene of a normal α-globin gene arrangement. This new variant represents the sixth described mutation at codon α91 and fourth on the α2 locus. As a result of the slight instability due to the significant role of the α91 residue in the α1β2 contact, the level of the Hb Zara variant was lower than levels observed for several stable variants codified by the α2 locus. [ABSTRACT FROM AUTHOR]

Neonatal cyanosis can result from a multitude of acquired and inherited causes. Cyanosis resulting from fetal M hemoglobin (Hb) variants is very rare. Only two Gγ variants causing methemoglobinemia and cyanosis in the newborn have been reported to date. Here we describe a novel fetal Hb variant, Hb F-Circleville [Gγ63(E7)His→Leu], associated with methemoglobinemia and cyanosis in the newborn. The patient's sister also had neonatal cyanosis at birth. [ABSTRACT FROM AUTHOR]

The Hb Gerland [α55(E4)Val→Ala] mutation has been described in the α2-globin gene. We report here the same mutation in the paralogous α1-globin gene. This variant was found in a healthy 18-month-old boy of Chinese origin. Abnormal hemoglobin (Hb) fractions were visible on isoelectric focusing (IEF) and cation exchange high performance liquid chromatography (HPLC), with elution patterns differing from one system to another. Direct sequencing of the α-globin genes revealed a GTT>GCT (Val→Ala) transversion at codon 55 of the α1-globin gene. We propose to name the variant encoded by the α1-globin gene Hb Gerland [A1], and the variant that is encoded by the α2-globin gene Hb Gerland [A2]. [ABSTRACT FROM AUTHOR]

In Hb J-Singapore, the α78(EF7)Asn→Asp and α79(EF8)Ala→Gly substitutions were initially thought to be genetic mutations. Subsequent studies on other similar hemoglobin variants suggested that the Asn→Asp change was a posttranslational modification. Nevertheless, lack of DNA evidence made it difficult to confirm the deamidation in Hb J-Singapore. We recently encountered a female patient with Hb J-Singapore trait. In this report, we present electrospray mass spectrometry and DNA data to confirm the α78(EF7)Asn→Asp is indeed a posttranslational modification. [ABSTRACT FROM AUTHOR]