دانلود رایگان مقاله حذف این فریم در پروتئین ریبوزومی S19 با کم خونی دیاموند-بلک فان

Abstract

Diamond-Blackfan anemia (DBA) is a congenital erythroid aplasia that usually presents as macrocytic anemia during infancy. Ribosomal protein S19 (RPS19) is identified as the first gene associated with DBA. RPS19 is mutated in 25% of DBA patients, but its role in DBA pathogenesis remains to be elucidated. We have identified a novel heterozygous frameshift mutation in RPS19 gene in a DBA child presenting with profound anemia after birth. A single nucleotide heterozygous deletion (C.251delG) results in frameshift in RPS19 gene in exon 4 at codon 84 with possible premature stop codon (p.Arg84LysfsX21). The mutant allele was not detected in her parents, indicating de novo mutation. Both alleles were expressed at the same level. Using an immunofluorescence technique, the mutated-type RPS19 expressions were mostly localized to entire nuclei with little staining for nucleoli and its intracellular localization significantly differed from the wild-type RPS19, which was localized to both nuclei and nucleoli. This type of a mutation could be very helpful in further understanding the role of the RPS19 protein in DBA pathogenesis.

3. Results and discussion

The patient in whom we found this novel mutation is a girl born to parents in the first uneventful pregnancy. Both parents were healthy. The delivery was induced at the 38th week of gestational age because of fetal distress, and a Caesarean section was performed. The developmental milestones were small for gestational age. The weight at birth was 2300 g (≥2500 g in infants born appropriate for gestational age -AGA); body length was 45 cm (50 cm in AGA-born infants); head circumference was 24 cm (32–34 cm in AGA-born infants). The patient was brought to our hospital with a history of conspicuously pale needing oxygen therapy when she was 2-months old. She had received one blood transfusion at 6th day of life for moderate anemia (hemoglobin 9.3 g/dl, hemoglobin N 14.5 g/dl within 10 days after birth ). There was no history of jaundice and the child showed no other associated anomalies. Blood count analyses revealed severe macrocytic anemia with normal counts of leukocytes and platelets. The data at the age of 8 weeks is summarized in Table 1. HbF was within normal limits. We could not perform erythrocyte adenosine deaminase (eADA) determination because she had received blood transfusion.