Hemoglobin Westmead α2122(H5)His←Glnβ2: A New Hemoglobin Variant with the Substitution in the α1β1Contact Area

Fleming, P. J.; Hughes, W. G.; Farmilo, R.K.; Wyatt, K.; Cooper, Wendy N.

doi:10.3109/03630268009042372

Cited by 31 publications

(8 citation statements)

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“…This indicates that the high frequency of HbH-WS may be confined to Guangxi province. Hb-WS was first reported by Fleming et al [16] in 1980. Hb-WS is prevalent in the Guangxi province of China [17], is mildly unstable [18], and cannot be detected by routine chromatography [19].…”

Section: Discussionmentioning

confidence: 99%

Hemoglobin H Disease in Guangxi Province, Southern China: Clinical Review of 357 Patients

et al. 2010

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The clinical characteristics of 357 patients with hemoglobin H (HbH) disease from the Guangxi province of Southern China were studied. One hundred and ninety-one (53.3%) patients were diagnosed with HbH-Constant Spring, 19 were diagnosed with HbH Westmead. Ten patients were shown to have coinherited HbH-Constant Spring/QS with a β-thalassemia mutation. Coinheritance of the β-thalassemia gene does not alleviate anemia (8.2 ± 2.3 vs. 7.6 ± 1.7 g/dl, p = 0.276), or influence age at diagnosis (20.2 ± 19.6 vs. 12.9 ± 11.0 years, p = 0.276). Ferritin levels were significantly higher in the group of patients with the nondeletional form of the disease (475 ± 719 vs. 249 ± 264 ng/ml, p = 0.005).

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Section: Discussionmentioning

confidence: 99%

Hemoglobin H Disease in Guangxi Province, Southern China: Clinical Review of 357 Patients

et al. 2010

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“…After the methodology was developed using wild-type hemoglobin, representative alpha and beta chain variants were analyzed to demonstrate the applicability of the method. For the purpose of this feasibility study we focused on two clinically relevant beta chain variants: Hb S (β6 Glu→Val), Hb C (β6 Glu→Lys) and a representative alpha chain variant Hb Westmead (α122His→Gln) 47 . MS characteristics of these samples including mass of intact protein and subsequent masses and assignments of tentative diagnostic ions are summarized in Table 2.…”

Section: Resultsmentioning

confidence: 99%

“…Lastly, we extended our approach to the characterization of an alpha chain variant, Hb Westmead (α122His→Gln) 47 , a variant that is common in Guangxi province in Southern China. The region of the MALDI-ISD mass spectrum containing the doubly charged ion corresponding to the intact alpha chain did not clearly indicate the presence of a variant (Figure 6(a) and 6(b)).…”

Section: Resultsmentioning

confidence: 99%

“…The region of the MALDI-ISD mass spectrum containing the doubly charged ion corresponding to the intact alpha chain did not clearly indicate the presence of a variant (Figure 6(a) and 6(b)). This is due to the low abundance of the variant which has been reported to be mildly unstable 47 . We observed this decrease in signal intensity of the variant chain in a previous ESI-MS analysis performed using ESI-MS on a Bruker Solarix FTMS (Supplemental Figure 6).…”

Section: Resultsmentioning

confidence: 99%

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MALDI-ISD Mass Spectrometry Analysis of Hemoglobin Variants: a Top-Down Approach to the Characterization of Hemoglobinopathies

Théberge

Dikler

Heckendorf

et al. 2015

J. Am. Soc. Mass Spectrom.

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Hemoglobinopathies are the most common inherited disorders in humans and are thus the target of screening programs worldwide. Over the past decade, mass spectrometry (MS) has gained a more important role as a clinical means to diagnose variants and a number of approaches have been proposed for characterization. Here we investigate the use of matrix-assisted laser desorption/ionization time-of-flight MS (MALDI-TOF MS) with sequencing using in-source decay (MALDI-ISD) for the characterization of Hb variants. We explored the effect of matrix selection using super DHB or 1,5-diaminonaphthalene on ISD fragment ion yield and distribution. MALDI-ISD MS of whole blood using super DHB simultaneously provided molecular weights for the alpha and beta chains, as well as extensive fragmentation in the form of sequence defining c-, (z+2)- and y-ion series. We observed sequence coverage on the first 70 amino acids positions from the N- and C-termini of the alpha and beta chains in a single experiment. An abundant beta chain N-terminal fragment ion corresponding to βc34 was determined to be a diagnostic marker ion for Hb S (β6 Glu→Val, sickle cell), Hb C (β6 Glu→Lys), and potentially for Hb E (β26 Glu→Lys). The MALDI-ISD analysis of Hb S and HbSC yielded mass shifts corresponding to the variants, demonstrating the potential for high-throughput screening. Characterization of an alpha chain variant, Hb Westmead (α122 His→Gln), generated fragments that established the location of the variant. This study is the first clinical application of MALDI-ISD MS for the determination and characterization of hemoglobin variants.

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“…Hb Westmead, first described by Fleming et al (4) in 1980 in a family who emigrated from Guangdong in Southern China to Australia, is one of the most common Hb variants in Guangxi Province (5,6). Seven out of 738 patients attending an Outpatient Clinic in a Center located in Guangxi, were found (by molecular analyses) to carry the Hb Westmead variant (5).…”

mentioning

confidence: 96%

Thalassemia Intermedia Due to Co‐inheritance of β⁰/β⁺‐Thalassemia and (– –^SEA)α‐Thalassemia/Hb Westmead [α122(H5)His > Gln (α2)] in a Chinese Family

et al. 2004

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Two brothers from a Chinese family with beta-thalassemia intermedia who harbor both alpha- and beta-globin gene defects are described. They are both compound heterozygous for codons 41/42 (-CTTT) beta0-thalassemia and nt - 28 (A > G) beta(+)-thalassemia mutations together with concurrent (- -SEA) alpha-thalassemia (SEA) deletion. One sibling also harbors Hb Westmead, giving an unusual genotype of beta0/beta(+)-thalassemia and (- -SEA) alpha-thalassemia/Hb Westmead. With respect to the age at presentation and transfusion requirement, this subject shows a milder clinical phenotype than his brother, most probably explainable by the presence of Hb Westmead in addition to the SEA deletion, which causes a further amelioration of the alpha-chain excess and hence a less severe disease. For areas with high prevalence of both alpha- and beta-thalassemia mutations, their interactions should always be considered in genotype phenotype correlation. Moreover, routine laboratory diagnostic strategy for non-deletional alpha-globin gene mutations in the Chinese may need to include Hb Westmead, as it is a common alpha-globin gene mutation in our population apart from Hb Constant Spring and Hb Quong Sze.

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Hemoglobin Westmead α₂122(H5)His←Gln_β₂: A New Hemoglobin Variant with the Substitution in the α₁β₁Contact Area

Cited by 31 publications

References 13 publications

Hemoglobin H Disease in Guangxi Province, Southern China: Clinical Review of 357 Patients

Hemoglobin H Disease in Guangxi Province, Southern China: Clinical Review of 357 Patients

MALDI-ISD Mass Spectrometry Analysis of Hemoglobin Variants: a Top-Down Approach to the Characterization of Hemoglobinopathies

Thalassemia Intermedia Due to Co‐inheritance of β⁰/β⁺‐Thalassemia and (– –^SEA)α‐Thalassemia/Hb Westmead [α122(H5)His > Gln (α2)] in a Chinese Family

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Hemoglobin Westmead α2122(H5)His←Glnβ2: A New Hemoglobin Variant with the Substitution in the α1β1Contact Area

Cited by 31 publications

References 13 publications

Hemoglobin H Disease in Guangxi Province, Southern China: Clinical Review of 357 Patients

Hemoglobin H Disease in Guangxi Province, Southern China: Clinical Review of 357 Patients

MALDI-ISD Mass Spectrometry Analysis of Hemoglobin Variants: a Top-Down Approach to the Characterization of Hemoglobinopathies

Thalassemia Intermedia Due to Co‐inheritance of β0/β+‐Thalassemia and (– –SEA)α‐Thalassemia/Hb Westmead [α122(H5)His > Gln (α2)] in a Chinese Family

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Hemoglobin Westmead α₂122(H5)His←Gln_β₂: A New Hemoglobin Variant with the Substitution in the α₁β₁Contact Area

Thalassemia Intermedia Due to Co‐inheritance of β⁰/β⁺‐Thalassemia and (– –^SEA)α‐Thalassemia/Hb Westmead [α122(H5)His > Gln (α2)] in a Chinese Family