Hb St. Jozef, A Val-->Leu N-terminal mutation leading to retention of the methionine, and partial acetylation found in the globin gene in Cis with a -alpha3.7 thalassemia deletion.
We report a new hemoglobin (Hb) variant found in a 6-year-old girl of Moroccan origin, living in the Dutch city of Gouda. The child was referred because of microcytic and hypochromic parameters. A normal zinc protoporphyirin (ZPP) value excluded iron deficiency and gap-polymerase chain reaction (gap-PCR) revealed a heterozygosity for the common -alpha(3.7) thalassemia deletion, partially justifying the hematological picture. The Hb pattern on alkaline electrophoresis and capillary electrophoresis was normal, while a fraction of 9% preceding the Hb A peak, remained visible on different high performance liquid chromatography (HPLC) devices. This fraction, located in front of the Hb A peak, is usually considered as a Hb A derivate that becomes more expressed in older samples. However, the sample was freshly collected and the peak unusually evident. Therefore, direct sequencing of the alpha-globin genes was performed revealing a GTG-->CTG transversion at codon 1 of the alpha1-globin gene or of the hybrid gene. This point mutation induces a single amino acid substitution from valine to leucine. Electrospray-mass spectrometry (ES-MS) analysis revealed, in addition to this substitution, that the N-terminal methionine was retained and that about 20% of the variant was acetylated. As expected for an association with a -alpha(3.7)-thalassemia (thal) deletion, the non acetylated and acetylated abnormal alpha chain amounted to 32% of the total alpha chains. Family studies revealed that the mutated codon was located in cis of the deletion.
Harteveld
Cornelis L
CL
The Hemoglobinopathies Laboratory, Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Versteegh
Florens G A
FG
van Leer
Eduard H G
EH
Starreveld
Jaap S
JS
Kok
Peter J M J
PJ
van Rooijen-Nijdam
Irene
I
van Delft
Peter
P
Zanella-Cleon
Isabelle
I
Becchi
Michel
M
Wajcman
Henri
H
Giordano
Piero C
PC
D000107:Acetylation; D019943:Amino Acid Substitution; D002648:Child; D005192:Family Health; D005260:Female; D005914:Globins / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D008715:Methionine; D009154:Mutation; D017384:Sequence Deletion; D013789:Thalassemia / Q000235:genetics*
D006455:Hemoglobins, Abnormal; C523159:hemoglobin St. Jozef; D005914:Globins; D008715:Methionine