ABSTRACT
We report three new alpha-thalassemia (thal) point mutations detected during newborn screening for hemoglobinopathies. The first mutation is a single nucleotide deletion (-A) that abolishes the translation initiation codon of the alpha2-globin gene, detected in a newborn of Hmong ethnicity who carried the Southeast Asian alpha(0)-thal deletion (alpha(T)alpha/- -(SEA)). The second mutation, a frameshift caused by a single nucleotide deletion in exon 2 of the alpha1-globin gene [codon 78 (-C)], was detected in a Black/Chinese newborn who also carried the Southeast Asian alpha0-thal deletion (alphaalpha(T)/- -(SEA)). The third mutation was a frameshift in exon 3 of the alpha2-globin gene, codons 113/114 (-C). This mutation was detected in a newborn who carried the 3.7 kb alpha(+)-thal deletion (alpha(T)alpha/-alpha(3.7)).
Subject(s)
Frameshift Mutation , Globins/genetics , Point Mutation , Sequence Deletion , alpha-Thalassemia/genetics , Amino Acid Sequence , Asian People/genetics , Black People/genetics , Chromosomes, Human, Pair 16/genetics , Codon/genetics , Codon, Nonsense , Ethnicity/genetics , Exons/genetics , Genotype , Globins/chemistry , Hemoglobins, Abnormal/genetics , Humans , Infant, Newborn , Male , Molecular Sequence Data , Neonatal ScreeningABSTRACT
In 1989, the Province of Ontario established a molecular diagnostic laboratory for carrier detection and prenatal diagnosis of hemoglobinopathies. Over the past 15 years, the laboratory has provided prenatal diagnosis for 672 pregnancies at-risk for severe hemoglobinopathies: 276 (41%) for homozygous beta-thalassemia or hemoglobin (Hb) E/beta-thalassemia, 211 (31%) for homozygous alpha 0-thalassemia (Hb Bart's hydrops fetalis), and/or Hb H disease, and 185 (28%) for various sickling disorders (Hb SS, Hb SC, Hb S/beta-thalassemia). Despite the availability of services for carrier screening, genetic counseling, and prenatal diagnosis, there has been only a modest reduction in the overall incidence of hemoglobinopathies in Ontario.
Subject(s)
Fetal Diseases/diagnosis , Hemoglobinopathies/diagnosis , Prenatal Diagnosis/statistics & numerical data , Adult , Amniocentesis/statistics & numerical data , Anemia, Sickle Cell/diagnosis , Anemia, Sickle Cell/epidemiology , Anemia, Sickle Cell/prevention & control , Chorionic Villi Sampling/statistics & numerical data , Ethnicity/genetics , Female , Fetal Diseases/epidemiology , Genetic Carrier Screening , Genetic Counseling , Gestational Age , Hemoglobinopathies/epidemiology , Hemoglobinopathies/prevention & control , Humans , Incidence , Male , Ontario/epidemiology , Pregnancy , Risk , Thalassemia/diagnosis , Thalassemia/epidemiology , Thalassemia/prevention & controlABSTRACT
We describe a case of beta-thalassemia (thal) trait in which the patient also carries a novel delta chain variant due to a missense mutation at amino acid codon 13 (GCC-->GAC, Ala-->Asp). The level of Hb A2 was not elevated, raising the potential for misdiagnosis.
Subject(s)
Hemoglobins, Abnormal/genetics , Mutation, Missense , Polymorphism, Single Nucleotide , beta-Thalassemia/genetics , Adult , Genotype , Hemoglobin A2/analysis , Hemoglobin A2/genetics , Humans , Male , Point MutationABSTRACT
We describe a case of Hb S/beta-thalassemia (thal) involving a 468 bp deletion that removes the beta-globin gene promoter but leaves the coding regions intact. This is the second report of this deletion, and our family study establishes that this deletion causes beta0-thal with unusually high levels of Hb A2 and Hb F. As with other genotypes involving deletions of the 5' region of the beta-globin gene, our patient had a mild form of Hb S/beta-thal.
Subject(s)
Hemoglobin A2/analysis , Hemoglobin, Sickle , Sequence Deletion , beta-Thalassemia/genetics , Child, Preschool , Family Health , Female , Fetal Hemoglobin/analysis , Humans , Promoter Regions, GeneticABSTRACT
A Chinese patient with Hb H (beta4) disease was found to be a compound heterozygote for a 2.4 kb alpha(+)-thalassemia (thal) deletion and the common Southeast Asian alpha0-thal deletion. The endpoints of the 2.4 kb deletion were identified by sequence analysis of the deletion junction. The deletion removes the entire alpha1-globin gene and leaves the alpha2-globin gene intact.
