HB Wayne, the Frameshift Variant with Extended α Chains Observed in a Caucasian Family from Alabama

Huisman, T. H. J.; Headlee, M. G.; Wilson, J. B.; Lam, H.; Johnson, S. E. N.; Webber, B. B.

doi:10.3109/03630268408996956

Cited by 7 publications

(4 citation statements)

References 14 publications

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“…In the third exon, other unstable variants were described; specifically, four variants create a very long α-chain: α2 cod90-93 (−8bp) or HBA2: c.272_279delAGCTTCGG (stop at codon 170) [48], α2 cod116-119 (−11bp) (stop at codon 166) [52]; Hb Pak Num Po (stop at codon 175) [55]; Hb Wayne (stop at codon 147) [57]. Patients compound heterozygous for these variants and an α0-thal or α+ -thal mutation are characterized by more severe phenotypes, including transfusion dependence.…”

Section: Mrna Variant In Globin Mutantsmentioning

confidence: 99%

mRNA Analysis of Frameshift Mutations with Stop Codon in the Last Exon: The Case of Hemoglobins Campania [α1 cod95 (−C)] and Sciacca [α1 cod109 (−C)]

et al. 2021

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An insertion or deletion of a nucleotide (nt) in the penultimate or the last exon can result in a frameshift and premature termination codon (PTC), giving rise to an unstable protein variant, showing a dominant phenotype. We described two α-globin mutants created by the deletion of a nucleotide in the penultimate or the last exon of the α1-globin gene: the Hb Campania or α1 cod95 (−C), causing a frameshift resulting in a PTC at codon 102, and the Hb Sciacca or α1 cod109 (−C), causing a frameshift and formation of a PTC at codon 133. The carriers showed α-thalassemia alterations (mild microcytosis with normal Hb A2) and lacked hemoglobin variants. The 3D model indicated the α-chain variants’ instability, due to the severe structural alterations with impairment of the chaperone alpha-hemoglobin stabilizing protein (AHSP) interaction. The qualitative and semiquantitative analyses of the α1mRNA from the reticulocytes of carriers highlighted a reduction in the variant cDNAs that constituted 34% (Hb Campania) and 15% (Hb Sciacca) of the total α1-globin cDNA, respectively. We developed a workflow for the in silico analysis of mechanisms triggering no-go decay, and its results suggested that the reduction in the variant mRNA was likely due to no-go decay caused by the presence of a rare triplet, and, in the case of Hb Sciacca, also by the mRNA’s secondary structure variation. It would be interesting to correlate the phenotype with the quantity of other frameshift mRNA variants, but very few data concerning α- and β-globin variants are available.

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Section: Mrna Variant In Globin Mutantsmentioning

confidence: 99%

mRNA Analysis of Frameshift Mutations with Stop Codon in the Last Exon: The Case of Hemoglobins Campania [α1 cod95 (−C)] and Sciacca [α1 cod109 (−C)]

et al. 2021

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“…This hemoglobin variant has been reported previously and referred to as hemoglobin Wayne. [10][11][12] After revealing the presence of this hemoglobin variant, boronate affinity chromatography was used to measure A1c, which was found to be 4.7%. This value was more consistent with reported blood glucose levels and further supported the fact the patient indeed did not have diabetes.…”

Section: Case Reportmentioning

confidence: 99%

Led Astray by Hemoglobin A1c

Chen

Diesburg-Stanwood

Bodor

et al. 2016

Journal of Investigative Medicine High Impact Case Reports

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Hemoglobin A1c (A1c) is used frequently to diagnose and treat diabetes mellitus. Therefore, it is important be aware of factors that may interfere with the accuracy of A1c measurements. This is a case of a rare hemoglobin variant that falsely elevated a nondiabetic patient’s A1c level and led to a misdiagnosis of diabetes. A 67-year-old male presented to endocrine clinic for further management after he was diagnosed with diabetes based on an elevated A1c of 10.7%, which is approximately equivalent to an average blood glucose of 260 mg/dL. Multiple repeat A1c levels remained >10%, but his home fasting and random glucose monitoring ranged from 92 to 130 mg/dL. Hemoglobin electrophoresis and subsequent genetic analysis diagnosed the patient with hemoglobin Wayne, a rare hemoglobin variant. This variant falsely elevates A1c levels when A1c is measured using cation-exchange high-performance liquid chromatography. When the boronate affinity method was applied instead, the patient’s A1c level was actually 4.7%. Though hemoglobin Wayne is clinically silent, this patient was erroneously diagnosed with diabetes and started on an antiglycemic medication. Due to this misdiagnosis, the patient was at risk of escalation in his “diabetes management” and hypoglycemia. Therefore, it is important that providers are aware of factors that may result in hemoglobin A1c inaccuracy including hemoglobin variants.

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“…The presence of an extra peak made interpretation of HbA 1c difficult as it overlapped with the HbA 1c peak, resulting in an estimate of 15.2% for the concentration of HbA 1c . The extra peak overlapped so considerably with the HbA 1c peak that the composite peak only exhibited extremely subtle indication of its dual nature [23]. Identification of the haemoglobin variant was by electrospray mass spectrometry which demonstrated that 18.5% of the haemoglobin was variant and that the HbA 1c concentration was 6.1%.…”

Section: Clinical Casesmentioning

confidence: 99%

“…This was first described in 1976 in a Caucasian neonate in Pike County, Central Georgia, whose grandparents originated from Birmingham, Alabama, USA [24]. Two other families have been reported; one a Caucasian family from Michigan [23] and another from Canada [25].…”

Section: Clinical Casesmentioning

confidence: 99%

The number of unexpected HbA_1c variants may be a greater problem in routine practice than is generally realized

Reynolds¹,

Twomey²,

Harvey³

et al. 2004

Diabetic Medicine

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HB Wayne, the Frameshift Variant with Extended α Chains Observed in a Caucasian Family from Alabama

Cited by 7 publications

References 14 publications

mRNA Analysis of Frameshift Mutations with Stop Codon in the Last Exon: The Case of Hemoglobins Campania [α1 cod95 (−C)] and Sciacca [α1 cod109 (−C)]

mRNA Analysis of Frameshift Mutations with Stop Codon in the Last Exon: The Case of Hemoglobins Campania [α1 cod95 (−C)] and Sciacca [α1 cod109 (−C)]

Led Astray by Hemoglobin A1c

The number of unexpected HbA_1c variants may be a greater problem in routine practice than is generally realized

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HB Wayne, the Frameshift Variant with Extended α Chains Observed in a Caucasian Family from Alabama

Cited by 7 publications

References 14 publications

mRNA Analysis of Frameshift Mutations with Stop Codon in the Last Exon: The Case of Hemoglobins Campania [α1 cod95 (−C)] and Sciacca [α1 cod109 (−C)]

mRNA Analysis of Frameshift Mutations with Stop Codon in the Last Exon: The Case of Hemoglobins Campania [α1 cod95 (−C)] and Sciacca [α1 cod109 (−C)]

Led Astray by Hemoglobin A1c

The number of unexpected HbA1c variants may be a greater problem in routine practice than is generally realized

Contact Info

Product

Resources

About

The number of unexpected HbA_1c variants may be a greater problem in routine practice than is generally realized