Hb fulton-georgia [α20(B1)His→Pro; HBA1: C.62A>C]: A new α-Globin variant coinherited with α-Thalassemia-2 (3.7 kb deletion) and Hb SC disease

Lina Zhuang, Niren Patel, Shanequa Bryant, Abdullah Kutlar, Ferdane Kutlar, Andrew N. Young

Research output: Contribution to journalArticle

Abstract

We report a novel hemoglobin (Hb) variant that we named Hb Fulton-Georgia, caused by a point mutation in exon 1/codon 20 of the α-globin gene [α20(B1)His→Pro; HBA1: c.62A>C]. This α chain variant was identified in an adult African-American female with Hb SC disease who was also heterozygous for the α-thalassemia-2 (α-thal-2) (3.7 kb deletion or αα/-α3.7). The Hb Fulton-Georgia mutation was located on the intact α1-globin gene not involved by α-thal-2. Molecular models indicated that the α20 residue of Hb Fulton-Georgia was the first amino acid of the B helix, and was not involved in α1/β1 or α1/β2 contacts in Hb S [β6(A3)Glu→Val; HBB: c.20A>T] or Hb C [β6(A3)Glu→Lys; HBB: c.19G>A] tetramers. Furthermore, the histidine→proline substitution at α20 did not disrupt the helical structure. High performance liquid chromatography (HPLC) detected Hb Fulton-Georgia in 16.0% of total Hb, consistent with inheritance on the α1 gene. Coinheritance of Hb Fulton-Georgia, heterozygous α-thal-2 and Hb SC disease was associated with a mild phenotype, consisting of microcytosis and anisocytosis, but no anemia or other hematological abnormality.

Original languageEnglish (US)
Pages (from-to)481-485
Number of pages5
JournalHemoglobin
Volume37
Issue number5
DOIs
StatePublished - Sep 12 2013

Fingerprint

Hemoglobin SC Disease
Thalassemia
Globins
Hemoglobins
Genes
Hemoglobin C
Sickle Hemoglobin
Molecular Models
High performance liquid chromatography
Point Mutation
Codon
African Americans
Anemia
Exons
Substitution reactions
High Pressure Liquid Chromatography
hemoglobin Fulton-Georgia
Phenotype
Amino Acids
Mutation

Keywords

  • α-Globin
  • Electrophoresis
  • Gene sequencing
  • Hemoglobin (Hb) variants
  • High performance liquid chromatography (HPLC)

ASJC Scopus subject areas

  • Hematology
  • Genetics(clinical)
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Hb fulton-georgia [α20(B1)His→Pro; HBA1 : C.62A>C]: A new α-Globin variant coinherited with α-Thalassemia-2 (3.7 kb deletion) and Hb SC disease. / Zhuang, Lina; Patel, Niren; Bryant, Shanequa; Kutlar, Abdullah; Kutlar, Ferdane; Young, Andrew N.

In: Hemoglobin, Vol. 37, No. 5, 12.09.2013, p. 481-485.

Research output: Contribution to journalArticle

Zhuang, Lina ; Patel, Niren ; Bryant, Shanequa ; Kutlar, Abdullah ; Kutlar, Ferdane ; Young, Andrew N. / Hb fulton-georgia [α20(B1)His→Pro; HBA1 : C.62A>C]: A new α-Globin variant coinherited with α-Thalassemia-2 (3.7 kb deletion) and Hb SC disease. In: Hemoglobin. 2013 ; Vol. 37, No. 5. pp. 481-485.
@article{f4a6a196942c480083949c5e5cea7342,
title = "Hb fulton-georgia [α20(B1)His→Pro; HBA1: C.62A>C]: A new α-Globin variant coinherited with α-Thalassemia-2 (3.7 kb deletion) and Hb SC disease",
abstract = "We report a novel hemoglobin (Hb) variant that we named Hb Fulton-Georgia, caused by a point mutation in exon 1/codon 20 of the α-globin gene [α20(B1)His→Pro; HBA1: c.62A>C]. This α chain variant was identified in an adult African-American female with Hb SC disease who was also heterozygous for the α-thalassemia-2 (α-thal-2) (3.7 kb deletion or αα/-α3.7). The Hb Fulton-Georgia mutation was located on the intact α1-globin gene not involved by α-thal-2. Molecular models indicated that the α20 residue of Hb Fulton-Georgia was the first amino acid of the B helix, and was not involved in α1/β1 or α1/β2 contacts in Hb S [β6(A3)Glu→Val; HBB: c.20A>T] or Hb C [β6(A3)Glu→Lys; HBB: c.19G>A] tetramers. Furthermore, the histidine→proline substitution at α20 did not disrupt the helical structure. High performance liquid chromatography (HPLC) detected Hb Fulton-Georgia in 16.0{\%} of total Hb, consistent with inheritance on the α1 gene. Coinheritance of Hb Fulton-Georgia, heterozygous α-thal-2 and Hb SC disease was associated with a mild phenotype, consisting of microcytosis and anisocytosis, but no anemia or other hematological abnormality.",
keywords = "α-Globin, Electrophoresis, Gene sequencing, Hemoglobin (Hb) variants, High performance liquid chromatography (HPLC)",
author = "Lina Zhuang and Niren Patel and Shanequa Bryant and Abdullah Kutlar and Ferdane Kutlar and Young, {Andrew N.}",
year = "2013",
month = "9",
day = "12",
doi = "10.3109/03630269.2013.810640",
language = "English (US)",
volume = "37",
pages = "481--485",
journal = "Hemoglobin",
issn = "0363-0269",
publisher = "Informa Healthcare",
number = "5",

}

TY - JOUR

T1 - Hb fulton-georgia [α20(B1)His→Pro; HBA1

T2 - C.62A>C]: A new α-Globin variant coinherited with α-Thalassemia-2 (3.7 kb deletion) and Hb SC disease

AU - Zhuang, Lina

AU - Patel, Niren

AU - Bryant, Shanequa

AU - Kutlar, Abdullah

AU - Kutlar, Ferdane

AU - Young, Andrew N.

PY - 2013/9/12

Y1 - 2013/9/12

N2 - We report a novel hemoglobin (Hb) variant that we named Hb Fulton-Georgia, caused by a point mutation in exon 1/codon 20 of the α-globin gene [α20(B1)His→Pro; HBA1: c.62A>C]. This α chain variant was identified in an adult African-American female with Hb SC disease who was also heterozygous for the α-thalassemia-2 (α-thal-2) (3.7 kb deletion or αα/-α3.7). The Hb Fulton-Georgia mutation was located on the intact α1-globin gene not involved by α-thal-2. Molecular models indicated that the α20 residue of Hb Fulton-Georgia was the first amino acid of the B helix, and was not involved in α1/β1 or α1/β2 contacts in Hb S [β6(A3)Glu→Val; HBB: c.20A>T] or Hb C [β6(A3)Glu→Lys; HBB: c.19G>A] tetramers. Furthermore, the histidine→proline substitution at α20 did not disrupt the helical structure. High performance liquid chromatography (HPLC) detected Hb Fulton-Georgia in 16.0% of total Hb, consistent with inheritance on the α1 gene. Coinheritance of Hb Fulton-Georgia, heterozygous α-thal-2 and Hb SC disease was associated with a mild phenotype, consisting of microcytosis and anisocytosis, but no anemia or other hematological abnormality.

AB - We report a novel hemoglobin (Hb) variant that we named Hb Fulton-Georgia, caused by a point mutation in exon 1/codon 20 of the α-globin gene [α20(B1)His→Pro; HBA1: c.62A>C]. This α chain variant was identified in an adult African-American female with Hb SC disease who was also heterozygous for the α-thalassemia-2 (α-thal-2) (3.7 kb deletion or αα/-α3.7). The Hb Fulton-Georgia mutation was located on the intact α1-globin gene not involved by α-thal-2. Molecular models indicated that the α20 residue of Hb Fulton-Georgia was the first amino acid of the B helix, and was not involved in α1/β1 or α1/β2 contacts in Hb S [β6(A3)Glu→Val; HBB: c.20A>T] or Hb C [β6(A3)Glu→Lys; HBB: c.19G>A] tetramers. Furthermore, the histidine→proline substitution at α20 did not disrupt the helical structure. High performance liquid chromatography (HPLC) detected Hb Fulton-Georgia in 16.0% of total Hb, consistent with inheritance on the α1 gene. Coinheritance of Hb Fulton-Georgia, heterozygous α-thal-2 and Hb SC disease was associated with a mild phenotype, consisting of microcytosis and anisocytosis, but no anemia or other hematological abnormality.

KW - α-Globin

KW - Electrophoresis

KW - Gene sequencing

KW - Hemoglobin (Hb) variants

KW - High performance liquid chromatography (HPLC)

UR - http://www.scopus.com/inward/record.url?scp=84883577882&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84883577882&partnerID=8YFLogxK

U2 - 10.3109/03630269.2013.810640

DO - 10.3109/03630269.2013.810640

M3 - Article

C2 - 24006930

AN - SCOPUS:84883577882

VL - 37

SP - 481

EP - 485

JO - Hemoglobin

JF - Hemoglobin

SN - 0363-0269

IS - 5

ER -