title: Is the poly A (T>C) mutation a causative factor for misdiagnosis in second trimester prenatal diagnosis of β-thalassemia by fetal blood analysis on high performance liquid chromatography?
abstract: We report the problems in diagnosis faced by two families referred for prenatal diagnosis of thalassemia where cordocentesis and fetal blood analysis by high performance liquid chromatography (HPLC) had to be done. The Hb A levels of the fetal blood measured by HPLC on the VARIANT™ Hemoglobin Testing System were 1.2 and 6.7%, respectively, suggestive of a heterozygous β-thalassemia (β-thal) fetus in the first case and a normal fetus in the second case. In one family, one of the parents had a borderline Hb A(2) level and in the other, one parent had normal RBC indices. However, DNA sequencing, done later, showed that in the first case the fetus was a compound heterozygote for the IVS-I-5 (G>C) and the polyadenylation signal site [poly A (T>C)] mutation, while in the second case, the fetus was homozygous for the poly A mutation. This emphasizes that characterization of β-thal mutations must be done whenever one of the parents has a borderline Hb A(2) level or normal RBC indices, and one should not rely on fetal blood analysis by HPLC for prenatal diagnosis of β-thal so as to avoid misdiagnosis.
authors.affiliation: National Institute of Immunohematology, King Edward Memorial Hospital Campus, Parel, Mumbai, India.
authors.forename: Khushnooma Y
authors.initials: KY
authors.lastname: Italia
authors.forename: Pratibha M
authors.initials: PM
authors.lastname: Sawant
authors.forename: Anita H
authors.initials: AH
authors.lastname: Nadkarni
authors.forename: Kanjaksha
authors.initials: K
authors.lastname: Ghosh
authors.forename: Roshan B
authors.initials: RB
authors.lastname: Colah
mesh_terms: D001483:Base Sequence; D015415:Biomarkers / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D017218:Cordocentesis; D004252:DNA Mutational Analysis; D003951:Diagnostic Errors; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D006443:Hemoglobin A2 / Q000032:analysis / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011061:Poly A / Q000097:blood / Q000235:genetics*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis; D017086:beta-Thalassemia / Q000097:blood / Q000175:diagnosis* / Q000235:genetics
chemical_list: D015415:Biomarkers; D011061:Poly A; D006443:Hemoglobin A2