A new case of congenital atransferrinemia with a novel splice site mutation: c.293-63del.

Abstract

Congenital atransferrinemia is an extremely rare autosomal recessive disorder resulting in the complete absence or extremely reduced amount of transferrin. In this study, we describe the first case of congenital atransferrinemia in Tunisia and the 18th patient in the reported data. The patient was referred to our hospital to explore a severe hypochromic and microcytic anemia. The laboratory evaluation including hematological and biochemical examination was performed in the proband and her parents. All exons of the transferrin gene were PCR amplified. The products were screened for mutations by direct sequencing. Based on laboratory and clinical findings, diagnosis of congenital atransferrinemia was confirmed. DNA sequencing revealed the presence of a novel homozygous deletion (c.293-63del) in the intron 13. This mutation is predicted to generate a higher score cryptic branch point leading to the production of an altered mRNA molecule. The second previously reported missense mutation p.Arg609Trp. Crystallographic structure analyzes demonstrate that the mutation would probably lead to significant conformational change not allowing the expression of transferrin protein. Current molecular characterization of this novel transferrin abnormality puts to the proof the variability in onset, first blood transfusion, and phenotypic expression in atransferrinemic patients.

• Authors: Rym Dabboubi, Yessine Amri, Salem Yahyaoui, Rahma Mahjoub, Chayma Abdelhafidh Sahli, Chaima Sahli, Sondess Hadj Fredj, Amina Bibi, Azza Sammoud, Taieb Messaoud
• Journal: European journal of medical genetics (Eur J Med Genet) Vol. 63 Issue 5 Pg. 103874 (May 2020) ISSN: 1878-0849 [Electronic] Netherlands
• PMID: 32028041 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2020 Elsevier Masson SAS. All rights reserved.

Chemical References

• RNA Splice Sites
• Transferrin

Topics

• Female
• Homozygote
• Humans
• Infant
• Metal Metabolism, Inborn Errors (genetics, pathology)
• Mutation
• Protein Domains
• RNA Splice Sites
• Transferrin (chemistry, deficiency, genetics, metabolism)