Hb Charlieu [alpha106(G13)Leu-->Pro (alpha1)]: a new phenotypically silent hemoglobin variant associated with a mild alpha-thalassemia phenotype.
A chronic microcytosis and hypochromia without any iron deficiency were observed in an 11-year-old boy of French Caucasian origin. The same hematological findings were also found for his mother. No abnormal hemoglobin (Hb) was detected using isoelectric focusing, cation exchange liquid chromatography and reversed phase liquid chromatography of the globin chains but DNA sequencing revealed a CTG>CCG transition at codon 106 (Leu-->Pro) of the alpha1-globin gene in both of them. As the alpha/beta mRNA ratios, determined by reverse-transcriptase real-time quantitative polymerase chain reaction (PCR), are not concordant with an alpha-thalassemia (alpha-thal) state, we hypothesize that the underlying physiopathologic mechanism is an assembling defect of the Hb Charlieu molecule, rather than an instability of the alpha(Charlieu) mRNA. Moreover, genetic counseling and patient information are required in this family to prevent potentially severe alpha-thalassemias in following generations.
Joly
Philippe
P
Unité de Pathologie Moléculaire du Globule Rouge, Fédération de Biochimie et de Biologie Spécialisée, Hôpital Edouard Herriot, Hospices Civils & Université Claude Bernard-Lyon 1, Lyon Cedex 03, France.
Szymanowicz
Anton
A
Neyron
Marie-Jeanne
MJ
Zine
Abdellah
A
Wajcman
Henri
H
Francina
Alain
A
D001483:Base Sequence; D002648:Child; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006455:Hemoglobins, Abnormal / Q000235:genetics; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055542:alpha-Globins / Q000235:genetics*; D017085:alpha-Thalassemia / Q000235:genetics* / Q000473:pathology; D055544:beta-Globins / Q000235:genetics
D003062:Codon; D006455:Hemoglobins, Abnormal; D055542:alpha-Globins; D055544:beta-Globins