title: The rare Hb Showa-Yakushiji [beta110(G12)Leu-->Pro, CTG-->CCG] in combination with an alpha gene triplication found in a Dutch patient during her first pregnancy examination.
abstract: We report a semi dominant beta-thalassemia (thal) phenotype caused by the rare Hb Showa-Yakushiji [beta110(G12)Leu-->Pro, CTG-->CCG] mutation in combination with an alpha gene triplication. This combination of two rare mutations was observed during hemoglobinopathy carrier diagnostics in a 26-year-old Dutch female at 9 weeks gestation, at the first pregnancy examination in the midwives practice. The partner was promptly examined and no abnormalities were found. The beta-thal trait was diagnosed by a standard high performance liquid chromatography (HPLC) procedure showing a normal separation but an elevated Hb A(2) level of 5.9% in the presence of pronounced hypochromic microcytic parameters and mild chronic hemolysis. Direct sequencing of the beta-globin genes was subsequently performed revealing a CTG-->CCG transition at codon 110. This rare mutation was previously described as two independent events in a few Japanese and Indian individuals. The mutation induces a Leu-->Pro substitution and the gene product is highly unstable. Gap-polymerase chain reaction (gap-PCR) revealed a heterozygosity for the alpha gene triplication as well. The excess of alpha-globin chains contributed only marginally to the hematological abnormalities of the patient and did not aggravate the phenotype to an intermediate level.
authors.affiliation: The Hemoglobinopathies Laboratory, Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. p.c.giordano@lumc.nl
authors.forename: Piero C
authors.initials: PC
authors.lastname: Giordano
authors.forename: Akosua
authors.initials: A
authors.lastname: Addo-Daaku
authors.forename: Margaretha J
authors.initials: MJ
authors.lastname: Sander
authors.forename: Irene
authors.initials: I
authors.lastname: van Rooijen-Nijdam
authors.forename: Peter
authors.initials: P
authors.lastname: van Delft
authors.forename: Cornelis L
authors.initials: CL
authors.lastname: Harteveld
authors.forename: Peter J M J
authors.initials: PJ
authors.lastname: Kok
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D007930:Leucine; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011392:Proline
chemical_list: D006455:Hemoglobins, Abnormal; C502559:hemoglobin Showa-Yakushiji; D004247:DNA; D011392:Proline; D007930:Leucine