Hb Southampton [B106(G8)Leu→PRO, CTG→CCG]\nin a Uruguayan woman
A 37 year-old-woman from the city of Montevideo, Uruguay, was referred to our laboratory\nwith a history of undiagnosed chronic hemolytic anemia since her childhood. The patient\nwas born at term after a normal pregnancy and delivery. At four months of age she was\nprescribed iron due to anemia. At eleven months of age, she had a respiratory tract\ninfection with anemia and jaundice. She was given her first transfusion at twenty-one\nmonths of age, when she had a new episode of respiratory tract infection with anemia and\nfever. Splenomegaly was detected at the time and she was misdiagnosed as beta\nthalassemia major based on her clinical data. The patient was continuously receiving\nblood transfusions until she was 16 years old (in 1990), when splenectomy was performed.\nPhysical examination revealed prominent skull, inferior maxilla and malar eminences as\nwell as palpebral fissures sloping upwards and backwards, with jaundice. This phenotype\nwas previously described in an Argentinian boy with Hb Southampton(.\nRed blood cell indices were electronically determined with an automated cell counter\n(Cell Dyn 3700). The screening for the most common structural hemoglobinopathies (Hb S,\nHb C) and the determination of the Hb A2 and Hb F levels were carried out in a Variant\nHbs high-performance liquid chromatography (HPLC) system (BioRad).\nDNA was extracted from a peripheral blood sample by standard methods. The seven most\ncommon deletional a-thalassemias (-a3.7, -a4.2, - -SEA, - -FIL, - -MED, -(a)20.5, and\n-THAI) were checked by multiplex polymerase chain reaction (PCR)(. The non-deletional mutations (aHpha,\naNcoI and aaNcoI ) were investigated by PCR and digestion with the restriction enzymes\nHphI and NcoI, respectively(. The beta-globin gene was amplified by\nPCR in two segments and sequenced in a ABI 3130 genetic analyzer (Applied Biosystems)\naccording to conditions already described(. The hematological data of the patient are shown in . The original microcytosis changed to\nmacrocytosis possibly due to the deficit of folic acid and vitamin B12 caused by the\ncontinuous regenerative activity of the bone marrow tissue; the levels of folic acid and\nvitamin B12 were undetectable.\nNo abnormal Hbs were detected by the Variant Hbs HPLC system and no alpha-thalassemia\nmutations were found. However, sequencing of the beta-gene showed a base substitution\n(T→C) in the second position of the 106th codon leading to a Leu→Pro\nsubstitution in the beta-globin chain corresponding to Hb Southampton.\nThis study was conducted in accordance with the Helsinki declaration as revised in 2008.\nThe patient gave written informed consent on participating in this study.