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Papers by Beverley Pullon
Hemoglobin, Jul 3, 2020
Abstract We report the identification of a large deletion of the α-globin gene cluster, which rem... more Abstract We report the identification of a large deletion of the α-globin gene cluster, which removed both HBA2 and HBA1 and included the region from HBZ to HBQ1 on chromosome 16 (16p13.3). The α0-thalassemia (α0-thal) deletion was discovered in an Indian family residing in New Zealand. The proband was a 3-month-old female, who presented with a Hb H disease of unknown molecular origin. Routine hematology showed marked hypochromic microcytic anemia, with numerous Hb H inclusion bodies. In the absence of iron deficiency, there was a strong clinical suspicion of α-thal. On initial screening using a multiplex gap polymerase chain reaction (gap-PCR), only the common rightward deletion (–α3.7) was detected. Investigation of the proband’s mother and father revealed the mother was heterozygous for the –α3.7 deletion, while none of the seven most common pathogenic α-thal deletions were detected in the father. Multiplex ligation-dependent probe amplification (MLPA) was employed to detect the presence of a novel α0-thal deletion in both the proband and her father. For the proband, the α0-thal deletion in combination with the –α3.7 deletion, eliminated three copies of HBA consistent with a clinical diagnosis of Hb H disease.
Hemoglobin, 2021
Hb Tacoma [β30(B12)Arg→Ser] is a missense variant that is caused by either an AGG>AGT or AGG&g... more Hb Tacoma [β30(B12)Arg→Ser] 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 β0-thalassemia (β0-thal). We propose that HBB: c.93G>C has been incorrectly assigned as β0-thal and discuss whether HBB: c.93G>T or HBB: c.93G>C should be classified as β+-thal instead, or as β-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.
Thalassemia Reports, May 24, 2017
We report a second occurrence of hemoglobin (Hb) Tyne, [β5 (A2) Pro>Ser] HBB:c.16C>T(p.Pro6Ser), ... more We report a second occurrence of hemoglobin (Hb) Tyne, [β5 (A2) Pro>Ser] HBB:c.16C>T(p.Pro6Ser), which like the first case was associated with normal hematology. We verified the variant was mildly unstable by showing it was greatly enriched in isopropanol precipitates. This minor instability accounts for the slightly decreased expression of the new β chain. The variant was picked up as an interfering component on HbA1c testing using cation exchange high performance liquid chromatography (HPLC). However, this may be an advantage in detecting electrophoretically silent variants. Furthermore, this report also highlights the importance of uneven or sloping baselines on HPLC, which could reflect the presence of a variant hemoglobin even in the presence of normal electrophoresis and full blood count.
Thalassemia Reports
Hemoglobin (Hb) Ottawa [α15(A13)Gly>Arg], also known as Hb Siam, results from GGT>CGT mutat... more Hemoglobin (Hb) Ottawa [α15(A13)Gly>Arg], also known as Hb Siam, results from GGT>CGT mutation in codon 15 of either HBA1 or HBA2. Hb Ottawa carriers typically have normal hematology but when the variant is coinherited with either α or β thalassemia, microcytic red cell indices were observed. The percentage of variant detected using routine methodology was variable (14-33%), with a higher percentage found when co-inherited with an abnormal α-globin genotype. The case presented here involved an Indian male with microcytic red cell indices, who was heterozygous for Hb Ottawa (HBA2:c.46G>C) and β+ thalassemia (HBB:c.-138C>T). This case represents the first reported finding of Hb Ottawa in the Indian population, as well as the first time capillary zone electrophoresis (CZE) has been used to identify the variant. The abnormal red cell indices were attributed to co-inheritance of β+ thalassemia mutation (HBB:c.-138C>T), which alters binding of transcriptional factors to the...
Journal of Laboratory Medicine
This is the first report of glycated haemoglobin (Hb) eluting in zone 10 on capillary zone electr... more This is the first report of glycated haemoglobin (Hb) eluting in zone 10 on capillary zone electrophoresis (CZE). In an index case, the aberrant peak was picked up during routine haemoglobinopathy testing using CZE. Mass spectrometry (MS) revealed this aberrant peak to be glycated Hb. Prompted by this initial case, a study was undertaken and the results showed that there was a strong positive linear relationship (R2 = 0.774; ρ = 0.88) between the level of glycated Hb peak eluting in zone 10 and the HbA1c value. Furthermore, all samples with an HbA1c of 54 mmol/mol or greater had an HbA1c peak eluting in zone 10.
Thalassemia Reports
Only four cases of Hb I-Toulouse have been reported to date. Current literature associates Hb I-T... more Only four cases of Hb I-Toulouse have been reported to date. Current literature associates Hb I-Toulouse in the heterozygote with a mild chronic hemolytic anemia. The variant is mildly unstable with a tendency to form metHb. The quantity of the variant in heterozygotes has been reported as varying between 33 to 40%. This report confirms the finding from a single case, that a reduced percentage of Hb IToulouse along with microcytosis can be attributed to the co-inheritance of an abnormal α globin genotype. This current case was found in a woman of Pacific People ethnicity residing in New Zealand. There is a high prevalence of α thalassemia in this ethnic group and New Zealand has the highest Pacific population in the world. Therefore, if a reduced percentage of Hb I-Toulouse is found with microcytosis and normal iron studies, co-inheritance with α thalassemia should be considered.
Clinical Biochemistry, 2012
Clinical Biochemistry, 2012
Objectives: To determine if a new haemoglobin (Hb) variant was the underlying cause of erythrocyt... more Objectives: To determine if a new haemoglobin (Hb) variant was the underlying cause of erythrocytosis in a subject with a high apparent HbA 1 c.
Hemoglobin, Jul 3, 2020
Abstract We report the identification of a large deletion of the α-globin gene cluster, which rem... more Abstract We report the identification of a large deletion of the α-globin gene cluster, which removed both HBA2 and HBA1 and included the region from HBZ to HBQ1 on chromosome 16 (16p13.3). The α0-thalassemia (α0-thal) deletion was discovered in an Indian family residing in New Zealand. The proband was a 3-month-old female, who presented with a Hb H disease of unknown molecular origin. Routine hematology showed marked hypochromic microcytic anemia, with numerous Hb H inclusion bodies. In the absence of iron deficiency, there was a strong clinical suspicion of α-thal. On initial screening using a multiplex gap polymerase chain reaction (gap-PCR), only the common rightward deletion (–α3.7) was detected. Investigation of the proband’s mother and father revealed the mother was heterozygous for the –α3.7 deletion, while none of the seven most common pathogenic α-thal deletions were detected in the father. Multiplex ligation-dependent probe amplification (MLPA) was employed to detect the presence of a novel α0-thal deletion in both the proband and her father. For the proband, the α0-thal deletion in combination with the –α3.7 deletion, eliminated three copies of HBA consistent with a clinical diagnosis of Hb H disease.
Hemoglobin, 2021
Hb Tacoma [β30(B12)Arg→Ser] is a missense variant that is caused by either an AGG>AGT or AGG&g... more Hb Tacoma [β30(B12)Arg→Ser] 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 β0-thalassemia (β0-thal). We propose that HBB: c.93G>C has been incorrectly assigned as β0-thal and discuss whether HBB: c.93G>T or HBB: c.93G>C should be classified as β+-thal instead, or as β-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.
Thalassemia Reports, May 24, 2017
We report a second occurrence of hemoglobin (Hb) Tyne, [β5 (A2) Pro>Ser] HBB:c.16C>T(p.Pro6Ser), ... more We report a second occurrence of hemoglobin (Hb) Tyne, [β5 (A2) Pro>Ser] HBB:c.16C>T(p.Pro6Ser), which like the first case was associated with normal hematology. We verified the variant was mildly unstable by showing it was greatly enriched in isopropanol precipitates. This minor instability accounts for the slightly decreased expression of the new β chain. The variant was picked up as an interfering component on HbA1c testing using cation exchange high performance liquid chromatography (HPLC). However, this may be an advantage in detecting electrophoretically silent variants. Furthermore, this report also highlights the importance of uneven or sloping baselines on HPLC, which could reflect the presence of a variant hemoglobin even in the presence of normal electrophoresis and full blood count.
Thalassemia Reports
Hemoglobin (Hb) Ottawa [α15(A13)Gly>Arg], also known as Hb Siam, results from GGT>CGT mutat... more Hemoglobin (Hb) Ottawa [α15(A13)Gly>Arg], also known as Hb Siam, results from GGT>CGT mutation in codon 15 of either HBA1 or HBA2. Hb Ottawa carriers typically have normal hematology but when the variant is coinherited with either α or β thalassemia, microcytic red cell indices were observed. The percentage of variant detected using routine methodology was variable (14-33%), with a higher percentage found when co-inherited with an abnormal α-globin genotype. The case presented here involved an Indian male with microcytic red cell indices, who was heterozygous for Hb Ottawa (HBA2:c.46G>C) and β+ thalassemia (HBB:c.-138C>T). This case represents the first reported finding of Hb Ottawa in the Indian population, as well as the first time capillary zone electrophoresis (CZE) has been used to identify the variant. The abnormal red cell indices were attributed to co-inheritance of β+ thalassemia mutation (HBB:c.-138C>T), which alters binding of transcriptional factors to the...
Journal of Laboratory Medicine
This is the first report of glycated haemoglobin (Hb) eluting in zone 10 on capillary zone electr... more This is the first report of glycated haemoglobin (Hb) eluting in zone 10 on capillary zone electrophoresis (CZE). In an index case, the aberrant peak was picked up during routine haemoglobinopathy testing using CZE. Mass spectrometry (MS) revealed this aberrant peak to be glycated Hb. Prompted by this initial case, a study was undertaken and the results showed that there was a strong positive linear relationship (R2 = 0.774; ρ = 0.88) between the level of glycated Hb peak eluting in zone 10 and the HbA1c value. Furthermore, all samples with an HbA1c of 54 mmol/mol or greater had an HbA1c peak eluting in zone 10.
Thalassemia Reports
Only four cases of Hb I-Toulouse have been reported to date. Current literature associates Hb I-T... more Only four cases of Hb I-Toulouse have been reported to date. Current literature associates Hb I-Toulouse in the heterozygote with a mild chronic hemolytic anemia. The variant is mildly unstable with a tendency to form metHb. The quantity of the variant in heterozygotes has been reported as varying between 33 to 40%. This report confirms the finding from a single case, that a reduced percentage of Hb IToulouse along with microcytosis can be attributed to the co-inheritance of an abnormal α globin genotype. This current case was found in a woman of Pacific People ethnicity residing in New Zealand. There is a high prevalence of α thalassemia in this ethnic group and New Zealand has the highest Pacific population in the world. Therefore, if a reduced percentage of Hb I-Toulouse is found with microcytosis and normal iron studies, co-inheritance with α thalassemia should be considered.
Clinical Biochemistry, 2012
Clinical Biochemistry, 2012
Objectives: To determine if a new haemoglobin (Hb) variant was the underlying cause of erythrocyt... more Objectives: To determine if a new haemoglobin (Hb) variant was the underlying cause of erythrocytosis in a subject with a high apparent HbA 1 c.