Hemoglobin Southampton (also known as hemoglobin Casper) is a rare hemoglobin structural variant resulting from a substitution of a leucine residue for proline at codon beta106 [beta106(G8)Leu→Pro, CTG→CCG]. It is very unstable and associated with severe hemolytic anemia. We detected this mutation in a 37-year-old Uruguayan woman with a history of severe chronic hemolytic anemia since her childhood. According to our knowledge this is the first time that this variant has been found in the Uruguayan population.352146147Perutz, M.F., Stereochemistry of cooperative effects in haemoglobin (1970) Nature, 228 (5273), pp. 726-739Hyde, R.D., Hall, M.D., Wiltshire, B.G., Lehmann, H., Haemoglobin Southampton, β106(G8)Leu→Pro: An unstable variant producing severe haemolysis (1972) Lancet, 2 (7788), pp. 1170-1172Koler, R.D., Jones, R.T., Bigley, R.H., Litt, M., Lovrien, E., Brooks, R., Lahey, M.E., Hemoglobin. Casper: β106 (G8) Leu→Proa contemporary mutation (1973) Am J Med, 55 (3), pp. 549-558Didkowskii, N.A., Idel'son, L.I., Filippova, A.V., Lemann, G., A new case of the unstable Hemoglobin Southampton-Casper (β106) (G8) leucine→proline (1976) Probl Gematol Pereliv Krovi, 21 (6), pp. 48-50. , RussianWajcman, H., Gacon, G., Labie, D., Koler, R.D., Jones, R.T., Isolation and functional characterization of hemoglobin Casper: β106 (G8) Leu replaced by Pro (1975) Biochemistry, 14 (22), pp. 5017-5020Heintz, N.H., Howard, P.L., Hemoglobin Southampton (Casper): Characterization of the base mutation (1989) Am J Hematol, 30 (1), pp. 1-3Eandi, S.E., Noguera, N.I., Sciuccati, G., Bonduel, M., Díaz, L., Staciuk, R., Hb Southampton [b106(G8)Leu→Pro, CTG→CCG] in an Argentinean boy (2006) Hemoglobin, 30 (3), pp. 401-403Avalos, V., Eandi, S., Pepe, C., Sciuccatia, G., García, N., Cervioa, C., [Severe hemolytic anemia due to hemoglobin Southampton]. Case report (2012) Arch Argent Pediatr, 110 (5), pp. e91-e94. , SpanishTan, A.S., Quah, T., Low, P., Chong, S.S., A rapid and reliable 7-deletion multiplex polymerase chain reaction assay for alpha-thalassemia (2001) Blood, 98 (1), pp. 250-251Hall, G.W., Thein, S., Newland, A., Chisholm, M., Traeger-Synodinos, J., Kanavakis, E., A base substitution (T-->C) in codon 29 of the alpha 2-globin gene causes alpha thalassaemia (1993) Br J Haematol, 85 (3), pp. 546-552Miranda, S.R., Fonseca, S., Figuereido, M., Yamamoto, M., Hb Köln [a2b298(FG5) val-met] identified by DNA analysis in a Brazilian family (1997) Braz J Genet, 20 (4)Williamson, D., The unstable haemoglobins (1993) Blood Rev, 7 (3), pp. 146-163Dacie, J.V., Lewis, S.M., (1995) Practical Haematology, , 8th ed. New York: Churchill Livingstone