Molecular identification of Sicilian (<FONT FACE=Symbol>dß)º-thalassemia associated with ß-thalassemia and hemoglobin S in Brazil</FONT>

Abstract

We describe the clinical and molecular characteristics of two unrelated Brazilian families with an association of the Sicilian form of (δß)º-thalassemia with hemoglobin S and ß-thalassemia. Direct sequencing of the ß-globin gene showed only the hemoglobin S mutation in patient 1 and the ß-thalassemia IVS1-110 in patient 2. The other allele was deleted in both patients and PCR of DNA samples of the breakpoint region of both patients showed a band of approximately 1,150 bp, expected to be observed in the DNA of carriers of Sicilian (δß)º-thalassemia. The nucleotide sequence of this fragment confirmed the Sicilian deletion. There are few reports concerning the Hb S/(δß)º-thalassemia association and patient 2 is the first reported case of Sicilian type of (δß)º-thalassemia in association with ß-thalassemia documented at the molecular level. The (δß)º-thalassemias are a rare group of disorders characterized, in the heterozygous state, by increased levels of fetal hemoglobin ranging from 5 to 15% during adulthood. This condition preserves some of the thalassemic phenotype, such as microcytic and hypochromic red blood cells, and is caused by extensive deletions involving a variable extent of the DNA segment in the ß-globin gene cluster (1).Heterozygous compound states for both (δß)º-and ß-thalassemia have been described in Italian (2,3), Greek (2,4,5) and Yugoslavian (6) populations. Although the clinical manifestations of these conditions are variable, the disorder is, in general, milder than homozygous ß-thalassemia major. The association of sickle-cell hemoglobinopathy and (δß)º-thalassemia is described as a relatively mild sickling disorder and has been observed in Italian (1), Greek (7), Arab (8) and AfroAmerican (9,10) individuals. Most of the reported cases have not been submitted to detailed DNA analysis and, to our knowledge, there is no description of these associations in the Brazilian population.We describe here the clinical and molecular characteristics of two unrelated Brazilian families with an association of the Sicilian form of (δß)º-thalassemia with hemoglobin S and ß-thalassemia.Hematological data and red blood cell

Screening for common β‐globin gene cluster deletions in Chinese individuals with increased hemoglobin F

“…Although high Hb F deletions in combination with β 0 ‐thalassemia point mutations usually lead to a nontransfusion‐dependent thalassemia intermedia condition, we were confronted with a compound heterozygous patient with the codons 41–42 (‐TCTT) (β 0 ) and Chinese ( A γδβ) 0 thalassemia , who suffered from a severe phenotype requiring blood transfusions. The thalassemia intermedia phenotype associated with δβ‐thalassemia and β‐thalassemia has also been described . Therefore, δβ‐thalassemia deletion screening would improve the chances of rapid identification of compound heterozygotes and the quality of genetic counseling.…”

Identification of patients with defects in the globin genes by analysing blood parameters and genetic study: Report of five cases

“…δβ-thalassemia is characterized by the occurrence of large deletions involving the δ and β globin genes [10] . Heterozygous carriers of δβ-thalassemia show HbF levels ranging from 4.0% to 18.6% [11,12] . Furthermore, even some hematological parameters of the patient's partner were not in the prefixed range (see Table 1).…”