Hb S-San Martin: A New Sickling Hemoglobin With Two Amino Acid Substitutions [β6(A3)Glu→Val;β105(G7)Leu→Pro] In An Argentinean Family

Abstract

A new sickling hemoglobin (Hb) detected in an Argentinean family from San Martín, Buenos Aires, Argentina, is hereby described. Two mutations were identified on the same β-globin gene resulting in a new variant named Hb San Martin. One mutation was found on exon 1, corresponding to Hb S [β6Glu→Val, GAG>GTG] and the second one on exon 3 at β105(G7)Leu→Pro, CTC>CCC. The replacement of leucine by proline will likely impair the structure breaking helix G and causing instability of the molecule and the clinical manifestations typical of unstable Hbs. The mutation at β105 seemed to be a de novo one in our patients, arising on a previously mutated gene, due to the fact that Hb S is the most frequent structural variant.

Non-S Sickling Hemoglobin Variants: Historical, Genetic, Diagnostic, and Clinical Perspectives

“…HbS-San Martin is the 12th non-S sickling Hb to be described. It was discovered in a 10-year-old boy in an Argentinean family from San Martin, Buenos Aires, Argentina as described by Feliu-Torres et al, 31 in 2010. HbS-San Martin is a double mutant characterized by the presence of one mutation on exon-1 [GAG>GTG] that corresponds to HbS [βGlu6Val] substitution, and the second mutation on exon-3 [CTC>CCC], which corresponds to βLeu105Pro substitution.…”

“…HbS-San Martin is a double mutant characterized by the presence of one mutation on exon-1 [GAG>GTG] that corresponds to HbS [βGlu6Val] substitution, and the second mutation on exon-3 [CTC>CCC], which corresponds to βLeu105Pro substitution. 31 In addition to giving positive solubility and sickling tests, HbS-San Martin migrated in similarity with HbS as depicted by alkaline cellulose and acid pH agar gel electrophoresis. 31 Moreover, heat stability and isopropanol tests were positive indicating that HbS-San Martin is an unstable Hb variant.…”

“… 31 In addition to giving positive solubility and sickling tests, HbS-San Martin migrated in similarity with HbS as depicted by alkaline cellulose and acid pH agar gel electrophoresis. 31 Moreover, heat stability and isopropanol tests were positive indicating that HbS-San Martin is an unstable Hb variant. 31 The index case was a simple heterozygote for the HbS-San Martin mutation, which he inherited from his mother, in whom the mutation might have occurred spontaneously.…”

“… 31 Moreover, heat stability and isopropanol tests were positive indicating that HbS-San Martin is an unstable Hb variant. 31 The index case was a simple heterozygote for the HbS-San Martin mutation, which he inherited from his mother, in whom the mutation might have occurred spontaneously. 31 Both the index case and his mother revealed the presence of pallor and jaundice, but neither had any history of pain or VOC.…”

“… 31 The index case was a simple heterozygote for the HbS-San Martin mutation, which he inherited from his mother, in whom the mutation might have occurred spontaneously. 31 Both the index case and his mother revealed the presence of pallor and jaundice, but neither had any history of pain or VOC. 31 These findings suggest that HbS-San Martin is recessive with respect to pain and VO symptoms.…”