RESUMO
OBJECTIVE: To evaluate the frequency of de novo monoallelic expression of the ANK1 gene in hereditary spherocytosis individuals appearing as recessive. STUDY DESIGN: We studied 40 unrelated children with spherocytosis and their normal parents. The genomic distribution of the ankyrin (AC)n dinucleotide repeats was evaluated in the patients showing combined ankyrin and spectrin deficiency. To search for the absence of mRNA derived from one of the two ANK1 genes, cDNA from the heterozygous patients was amplified using polymerase chain reaction. This was analyzed for the (AC)n dinucleotide repeats. RESULTS: Thirty-three hereditary spherocytosis subjects had variable degrees of combined ankyrin and spectrin reduction; 19 were found to be heterozygous for the AC repeat lengths and were further studied. In 12, we found a cDNA polymerase chain reaction product from one ankyrin gene alone. These findings strongly suggested the nonexpression of one of the two ANK1 genes because of the de novo mutational events. CONCLUSION: The de novo loss of an ankyrin allele expression is a frequent cause of hereditary spherocytosis in children with normal parents. Therefore the category of genuinely recessive hereditary spherocytosis cases is further reduced compared with spherocytosis cases because of de novo mutations. The determination of the (AC)n microsatellite polymorphisms appears as a helpful and reliable tool for the discrimination between these two categories.
Assuntos
Anquirinas/genética , Mutação , Esferocitose Hereditária/genética , Adolescente , Criança , Pré-Escolar , Repetições de Dinucleotídeos , Feminino , Genes Recessivos , Humanos , Lactente , Masculino , Linhagem , Reação em Cadeia da Polimerase , RNA Mensageiro/análiseRESUMO
Phototherapy was employed in treatment of newborn infants with erythrocyte G-6-PD deficiency whose serum bilirubin concentrations exceeded 10 mg/100 ml on the second or third day of life. Exchange transfusions were required for two of the 12 treated babies and for six of the 12 control infants. It is noteworthy that exposure to light did not affect the erythrocyte GSH content nor did it increase hemolysis.