The Experts below are selected from a list of 3846 Experts worldwide ranked by ideXlab platform
James D Hoyer - One of the best experts on this subject based on the ideXlab platform.
-
interpreting sulfHemoglobin and metHemoglobin in patients with cyanosis an overview of patients with m Hemoglobin Variants
International Journal of Laboratory Hematology, 2021Co-Authors: Aruna Rangan, Kenneth C Swanson, Michelle E Savedra, Camila Dergamlarson, Jessica Szuberski, Tavanna R Porter, Sarah E Brunker, Min Shi, Phuong L Nguyen, James D HoyerAbstract:Introduction MetHemoglobin (MetHb) and sulfHemoglobin (SHb) measurements are useful in the evaluation of cyanosis. When one or both values are elevated, additional analysis is important to establish the etiology of the disorder. MetHemoglobinemia occurs from acquired or hereditary causes with diverse treatment considerations, while true sulfHemoglobinemia is only acquired and treatment is restricted to toxin removal. Some toxic exposures can result in a dual increase in MetHb and SHb. Hereditary conditions, such as M-Hemoglobin Variants (M-Hbs), can result in increased MetHb and/or SHb values but are clinically compensated and do not require treatment if they are cyanotic but otherwise clinically well. Methods Herein, we report 53 Hemoglobin Variant cases that have associated MetHb and SHb levels measured by an adapted Evelyn-Malloy laboratory assay method. Results Our data indicate M-Hbs cause variable patterns of MetHb and SHb elevation in a fairly reproducible pattern for the particular Variant. In particular, α globin chain M-Hbs can mimic acquired sulfHemoglobinemia due to an isolated increased SHb value. Conclusion If the patient appears clinically well other than cyanosis, M-Hbs should be considered early in the evaluation process to differentiate from acquired conditions to avoid unnecessary testing and treatment regimens and prompt genetic counseling.
-
hb gibbon β124 h2 pro thr hbb c 373c a p p125t an asymptomatic novel Hemoglobin Variant detected by newborn screening
Hemoglobin, 2019Co-Authors: Alejandro Wolf, James D Hoyer, Joseph Rohr, Catalina Amador, Lois J Starr, James B FordAbstract:AbstractWe describe here a previously unreported Hemoglobin (Hb) Variant, Hb Gibbon [β124(H2)Pro→Thr (HBB: c.373C>A, p.P125T)] detected by newborn Hb screening in a term male with no family history...
-
a novel β globin chain Hemoglobin Variant hb allentown β137 h15 val trp gtg tgg hbb c 412_413delinstg p val138trp associated with low oxygen saturation intermittent aplastic crises and splenomegaly
Hemoglobin, 2016Co-Authors: Anderson B Collier, James D Hoyer, Kenneth C Swanson, Lea M Coon, Philip Monteleone, Samuel Umaru, Jennifer L OliveiraAbstract:AbstractHemoglobin (Hb) Variants may be associated with low oxygen saturation and exacerbated episodes of anemia from common stressors such as viral infections. These attributes frequently cause increased clinical concern and unnecessary and expensive testing if not considered early in the evaluation of the patient. Some clinically significant Hb Variants result in a normal Hb electrophoresis result, which can be method-dependent. Herein we describe a patient with low oxygen saturation and a history of hemolytic anemia who was subsequently found to carry a novel, unstable β-globin Variant that we have named Hb Allentown [β137(H15)Val→Trp (GTG>TGG) HBB: c.412_413delinsTG, p.Val138Trp] for the place of identification of the Variant. Hb Allentown is formed by a rare double nucleotide substitution within the same codon. Additionally, positive identification of rare Hb Variants characterized by a single method is discouraged, as the Hb Variant was misclassified as Hb S-South End or β6(A3)Glu→Val;β132(H10)Lys→A...
-
a novel β globin chain Hemoglobin Variant hb allentown β137 h15 val trp gtg tgg hbb c 412_413delinstg p val138trp associated with low oxygen saturation intermittent aplastic crises and splenomegaly
Hemoglobin, 2016Co-Authors: Anderson B Collier, James D Hoyer, Kenneth C Swanson, Lea M Coon, Samuel Umaru, Philip M Monteleone, Jennifer L OliveiraAbstract:Hemoglobin (Hb) Variants may be associated with low oxygen saturation and exacerbated episodes of anemia from common stressors such as viral infections. These attributes frequently cause increased clinical concern and unnecessary and expensive testing if not considered early in the evaluation of the patient. Some clinically significant Hb Variants result in a normal Hb electrophoresis result, which can be method-dependent. Herein we describe a patient with low oxygen saturation and a history of hemolytic anemia who was subsequently found to carry a novel, unstable β-globin Variant that we have named Hb Allentown [β137(H15)Val→Trp (GTG>TGG) HBB: c.412_413delinsTG, p.Val138Trp] for the place of identification of the Variant. Hb Allentown is formed by a rare double nucleotide substitution within the same codon. Additionally, positive identification of rare Hb Variants characterized by a single method is discouraged, as the Hb Variant was misclassified as Hb S-South End or β6(A3)Glu→Val;β132(H10)Lys→Asn (HBB: c.[20A > T;399A > C]) by the initial laboratory.
-
hb grand junction hbb c 348_349delinsg p his117ilefsx42 a new hyperunstable Hemoglobin Variant
Hemoglobin, 2014Co-Authors: Michael W Kent, Jennifer L Oliveira, James D Hoyer, Kenneth C Swanson, Michelle L Kluge, Brian D Dawson, Xiayuan Liang, Tyler J Winkler, Charles W Breaux, Rachel LacountAbstract:AbstractHyperunstable Hemoglobinopathy (HUH) [dominantly inherited β-thalassemia (β-thal)] is a relatively rare form of congenital hemolytic anemia in which mutations occur in the genes encoding for α and β chains, or both chains of the Hemoglobin (Hb) molecule. We describe two Hispanic adolescents with a new unstable Hb Variant (HBB: c.348_349delinsG; p.His117IlefsX42), resulting from a frameshift mutation at codons 115/116 of the β-globin gene. Both patients also have a 3.7 kb deletion on one α gene, leading to a decreased imbalance between α and β chain formation, and subsequently a milder phenotype than that seen in other hyperunstable Hb Variants.
Jennifer L Oliveira - One of the best experts on this subject based on the ideXlab platform.
-
Hemoglobin sunshine seth a case report of low oxygen affinity Hemoglobinopathy
Case reports in pediatrics, 2020Co-Authors: Leah S Heidenreich, Peter J Holmberg, Jennifer L Oliveira, Vilmarie RodriguezAbstract:Pulse oximetry is routinely used in the newborn nursery for clinical monitoring and to detect critical congenital heart disease. The differential diagnoses for reduced peripheral oxygen saturation in an infant include congenital heart disease, respiratory distress syndrome, transient tachypnea of the newborn, persistent pulmonary hypertension of the newborn, meconium aspiration syndrome, pneumonia, pneumothorax, and sepsis. The diagnostic evaluation for neonatal hypoxemia can be invasive and expensive. When this evaluation is unrevealing, other interventions may be tried without clear benefit to the patient, including, but not limited to, supplemental oxygen. Therefore, it is important to consider alternative, albeit rare, diagnoses, including Hemoglobinopathies with abnormal oxygen binding properties. Mutations in the structure of alpha- and beta-globin chains can alter the affinity of Hemoglobin for oxygen, and changes in oxygen affinity may result in changes in the oxygen saturation detected by pulse oximetry. These changes may or may not be of clinical significance. This case report describes Hemoglobin Sunshine Seth, a rare low-oxygen-affinity Hemoglobin Variant presenting as reduced peripheral oxygen saturation in an otherwise well-appearing infant male.
-
a novel β globin chain Hemoglobin Variant hb allentown β137 h15 val trp gtg tgg hbb c 412_413delinstg p val138trp associated with low oxygen saturation intermittent aplastic crises and splenomegaly
Hemoglobin, 2016Co-Authors: Anderson B Collier, James D Hoyer, Kenneth C Swanson, Lea M Coon, Philip Monteleone, Samuel Umaru, Jennifer L OliveiraAbstract:AbstractHemoglobin (Hb) Variants may be associated with low oxygen saturation and exacerbated episodes of anemia from common stressors such as viral infections. These attributes frequently cause increased clinical concern and unnecessary and expensive testing if not considered early in the evaluation of the patient. Some clinically significant Hb Variants result in a normal Hb electrophoresis result, which can be method-dependent. Herein we describe a patient with low oxygen saturation and a history of hemolytic anemia who was subsequently found to carry a novel, unstable β-globin Variant that we have named Hb Allentown [β137(H15)Val→Trp (GTG>TGG) HBB: c.412_413delinsTG, p.Val138Trp] for the place of identification of the Variant. Hb Allentown is formed by a rare double nucleotide substitution within the same codon. Additionally, positive identification of rare Hb Variants characterized by a single method is discouraged, as the Hb Variant was misclassified as Hb S-South End or β6(A3)Glu→Val;β132(H10)Lys→A...
-
a novel β globin chain Hemoglobin Variant hb allentown β137 h15 val trp gtg tgg hbb c 412_413delinstg p val138trp associated with low oxygen saturation intermittent aplastic crises and splenomegaly
Hemoglobin, 2016Co-Authors: Anderson B Collier, James D Hoyer, Kenneth C Swanson, Lea M Coon, Samuel Umaru, Philip M Monteleone, Jennifer L OliveiraAbstract:Hemoglobin (Hb) Variants may be associated with low oxygen saturation and exacerbated episodes of anemia from common stressors such as viral infections. These attributes frequently cause increased clinical concern and unnecessary and expensive testing if not considered early in the evaluation of the patient. Some clinically significant Hb Variants result in a normal Hb electrophoresis result, which can be method-dependent. Herein we describe a patient with low oxygen saturation and a history of hemolytic anemia who was subsequently found to carry a novel, unstable β-globin Variant that we have named Hb Allentown [β137(H15)Val→Trp (GTG>TGG) HBB: c.412_413delinsTG, p.Val138Trp] for the place of identification of the Variant. Hb Allentown is formed by a rare double nucleotide substitution within the same codon. Additionally, positive identification of rare Hb Variants characterized by a single method is discouraged, as the Hb Variant was misclassified as Hb S-South End or β6(A3)Glu→Val;β132(H10)Lys→Asn (HBB: c.[20A > T;399A > C]) by the initial laboratory.
-
hb grand junction hbb c 348_349delinsg p his117ilefsx42 a new hyperunstable Hemoglobin Variant
Hemoglobin, 2014Co-Authors: Michael W Kent, Jennifer L Oliveira, James D Hoyer, Kenneth C Swanson, Michelle L Kluge, Brian D Dawson, Xiayuan Liang, Tyler J Winkler, Charles W Breaux, Rachel LacountAbstract:AbstractHyperunstable Hemoglobinopathy (HUH) [dominantly inherited β-thalassemia (β-thal)] is a relatively rare form of congenital hemolytic anemia in which mutations occur in the genes encoding for α and β chains, or both chains of the Hemoglobin (Hb) molecule. We describe two Hispanic adolescents with a new unstable Hb Variant (HBB: c.348_349delinsG; p.His117IlefsX42), resulting from a frameshift mutation at codons 115/116 of the β-globin gene. Both patients also have a 3.7 kb deletion on one α gene, leading to a decreased imbalance between α and β chain formation, and subsequently a milder phenotype than that seen in other hyperunstable Hb Variants.
-
hb nebraska β86 f2 ala ile hbb c 259g a 260c t a unique high oxygen affinity Hemoglobin Variant with a double nucleotide substitution within the same codon
Hemoglobin, 2011Co-Authors: James D Hoyer, Patricia Wendt, William J Hogan, Jennifer L OliveiraAbstract:A new high oxygen affinity Hemoglobin (Hb) Variant, Hb Nebraska [β86(F2)Ala→Ile, GCC>ATC; HGVS: HBB: c.259G>A;260C>T] is reported. This Variant was not identified by routine methods and was only suspected due to erythrocytosis and an abnormal p50 value. The Variant was analyzed by DNA sequencing and mass spectrometry (MS). The β chain Variant is unusual in that it has two nucleotide substitutions occurring at the same codon.
David M Lubman - One of the best experts on this subject based on the ideXlab platform.
-
use of a polybrene capillary coating in capillary electrophoresis for rapid analysis of Hemoglobin Variants with on line detection via an ion trap storage reflectron time of flight mass spectrometer
Analytical Chemistry, 1997Co-Authors: Michael X Li, Jing Tao Wu, David M LubmanAbstract:A polybrene capillary coating in capillary electrophoresis (CE) has been used for rapid analysis of Hemoglobin Variant digests. The use of the polybrene capillary coating has allowed sufficient separation to resolve the large number of digest products formed upon tryptic digestion of the whole protein, so that prior separation of the Hemoglobin α and β chains is not required. The resolution of the digest peaks obtained by CE is sufficient so that even single amino acid substitutions can easily be detected using UV absorption detection. The digest is further analyzed by capillary electrophoresis separation with on-line detection using electrospray ionization interfaced to the ion trap storage/reflectron time of flight device (CE/ESI-IT/reTOF), where a comparison of the total ion electropherograms and mass spectra of the mutant and normal Hemoglobins can detect the presence of a mutation site. The CE separation and mass analysis can be accomplished in typically 10−15 min. The unique capability of the CE/ESI...
-
use of a polybrene capillary coating in capillary electrophoresis for rapid analysis of Hemoglobin Variants with on line detection via an ion trap storage reflectron time of flight mass spectrometer
Analytical Chemistry, 1997Co-Authors: Lin Liu, David M LubmanAbstract:A polybrene capillary coating in capillary electrophoresis (CE) has been used for rapid analysis of Hemoglobin Variant digests. The use of the polybrene capillary coating has allowed sufficient separation to resolve the large number of digest products formed upon tryptic digestion of the whole protein, so that prior separation of the Hemoglobin α and β chains is not required. The resolution of the digest peaks obtained by CE is sufficient so that even single amino acid substitutions can easily be detected using UV absorption detection. The digest is further analyzed by capillary electrophoresis separation with on-line detection using electrospray ionization interfaced to the ion trap storage/reflectron time of flight device (CE/ESI-IT/reTOF), where a comparison of the total ion electropherograms and mass spectra of the mutant and normal Hemoglobins can detect the presence of a mutation site. The CE separation and mass analysis can be accomplished in typically 10−15 min. The unique capability of the CE/ESI...
Hideaki Moriyama - One of the best experts on this subject based on the ideXlab platform.
-
alteration of the α1β2 α2β1 subunit interface contributes to the increased Hemoglobin oxygen affinity of high altitude deer mice
PLOS ONE, 2017Co-Authors: Noriko Inoguchi, Nobuhiro Mizuno, Seiki Baba, Takashi Kumasaka, Chandrasekhar Natarajan, Jay F. Storz, Hideaki MoriyamaAbstract:BACKGROUND: Deer mice (Peromyscus maniculatus) that are native to high altitudes in the Rocky Mountains have evolved Hemoglobins with an increased oxygen-binding affinity relative to those of lowland conspecifics. To elucidate the molecular mechanisms responsible for the evolved increase in Hemoglobin-oxygen affinity, the crystal structure of the highland Hemoglobin Variant was solved and compared with the previously reported structure for the lowland Variant. RESULTS: Highland Hemoglobin yielded at least two crystal types, in which the longest axes were 507 and 230 A. Using the smaller unit cell crystal, the structure was solved at 2.2 A resolution. The asymmetric unit contained two tetrameric Hemoglobin molecules. CONCLUSIONS: The analyses revealed that αPro50 in the highland Hemoglobin Variant promoted a stable interaction between αHis45 and heme that was not seen in the αHis50 lowland Variant. The αPro50 mutation also altered the nature of atomic contacts at the α1β2/α2β1 intersubunit interfaces. These results demonstrate how affinity-altering changes in intersubunit interactions can be produced by mutations at structurally remote sites.
-
Alteration of the α1β2/α2β1 subunit interface contributes to the increased Hemoglobin-oxygen affinity of high-altitude deer mice
2017Co-Authors: Noriko Inoguchi, Nobuhiro Mizuno, Seiki Baba, Takashi Kumasaka, Chandrasekhar Natarajan, Jay F. Storz, Hideaki MoriyamaAbstract:BackgroundDeer mice (Peromyscus maniculatus) that are native to high altitudes in the Rocky Mountains have evolved Hemoglobins with an increased oxygen-binding affinity relative to those of lowland conspecifics. To elucidate the molecular mechanisms responsible for the evolved increase in Hemoglobin-oxygen affinity, the crystal structure of the highland Hemoglobin Variant was solved and compared with the previously reported structure for the lowland Variant.ResultsHighland Hemoglobin yielded at least two crystal types, in which the longest axes were 507 and 230 Å. Using the smaller unit cell crystal, the structure was solved at 2.2 Å resolution. The asymmetric unit contained two tetrameric Hemoglobin molecules.ConclusionsThe analyses revealed that αPro50 in the highland Hemoglobin Variant promoted a stable interaction between αHis45 and heme that was not seen in the αHis50 lowland Variant. The αPro50 mutation also altered the nature of atomic contacts at the α1β2/α2β1 intersubunit interfaces. These results demonstrate how affinity-altering changes in intersubunit interactions can be produced by mutations at structurally remote sites.
John S Waye - One of the best experts on this subject based on the ideXlab platform.
-
novel high oxygen affinity Hemoglobin Variant in a patient with polycythemia hb kennisis β85 f1 phe leu ttt ttg hbb c 258t g
Hemoglobin, 2020Co-Authors: John Chinawaeze Aneke, Ibrahim Al Nabhani, Madeleine Verhovsek, Leona C Rudinskas, John S WayeAbstract:AbstractWe 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...
-
hb north york beta 117 g19 his asp a new beta chain Hemoglobin Variant
Hemoglobin, 2009Co-Authors: John S Waye, Lynda Walker, Lisa M Nakamura, Andrew McfarlaneAbstract:Routine Hemoglobin (Hb) analysis identified a new β chain Hb Variant in an Iranian woman, who otherwise had normal hematological indices. Sequence analysis demonstrated that the Hb Variant was due to a missense mutation at amino acid codon 117 (CAC>GAC, His→Asp) of the β-globin gene.
-
hb north york beta 117 g19 his asp a new beta chain Hemoglobin Variant
Hemoglobin, 2009Co-Authors: John S Waye, Lynda Walker, Lisa M Nakamura, Barry Eng, Andrew McfarlaneAbstract:Routine Hemoglobin (Hb) analysis identified a new beta chain Hb Variant in an Iranian woman, who otherwise had normal hematological indices. Sequence analysis demonstrated that the Hb Variant was due to a missense mutation at amino acid codon 117 (CAC>GAC, His-->Asp) of the beta-globin gene.
-
identification of a new delta chain Hemoglobin Variant in a beta thalassemia carrier hb a2 mumc delta13 a10 ala asp
Hemoglobin, 2005Co-Authors: Lynda Walker, Andrew Mcfarlane, Barry Eng, Margie Patterson, John S WayeAbstract:We describe a case of beta-thalassemia (thal) trait in which the patient also carries a novel delta chain Variant due to a missense mutation at amino acid codon 13 (GCC-->GAC, Ala-->Asp). The level of Hb A2 was not elevated, raising the potential for misdiagnosis.
-
beta thalassemia in association with a new delta chain Hemoglobin Variant delta116 g18 arg leu implications for carrier screening and prenatal diagnosis
American Journal of Hematology, 2003Co-Authors: David H K Chui, John S Waye, Lynda Walker, Lisa M Nakamura, Barry Eng, Margaret Patterson, John D Lafferty, Suili YongAbstract:We describe a complicated genetic counseling and prenatal diagnostic case involving an East Indian couple that had lost two consecutive pregnancies. Hemoglobinopathy screening was conducted to investigate the possibility of Hb Bart's hydrops fetalis or Hb H hydrops fetalis. The initial work-up indicated that alpha-thalassemia was not a contributing factor, with both parents being carriers of single gene deletions (-alpha(3.7)/alphaalpha). However, the Hb electrophoresis results indicated that the couple might be at risk for having children with Hb E/Hb Lepore disease. Subsequent DNA testing demonstrated that the father carried the Hb E mutation, but failed to confirm that the mother carries the Hb Lepore deletion. Sequence analysis revealed that the mother was heterozygous for a common East Indian beta(0)-thalassemia mutation, yet had a normal level of Hb A(2). The mother also carried a previously unreported missense mutation of the delta-globin gene, in cis with the beta(0)-thalassemia mutation, which gave rise to the minor Hb Variant originally misidentified as Hb Lepore. This case illustrates the importance of comprehensive molecular analyses for accurate assessment of genetic risks for Hemoglobinopathy syndromes.