Production of An Incomplete Protein and Diamond Blockfan Anemia Disease Due to a New Nonsense Mutation in RPS19 Gene

Subject Areas : Journal of Animal Biology

Javad  Roodgar Saffari ¹ (Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran)
Mohamad Mahdi  Forghanifard ² (Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran)
Vajihe  Zarrinpour ³ (Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran)

Received: 2022-09-14 Accepted : 2023-01-08 Published : 2023-08-23

Keywords: RPS19, Whole Exome Sequencing, Diamond-Blackfan Anemia,

Abstract :

Congenital hypoplastic anemia or Diamond-Blackfan anemia (DBA) usually occurs in the first year of life, and most patients with DBA survive until the age of six. For every one million live births, five to seven babies are affected by this disease. In 80-85% of cases, this disorder is caused by mutation of the ribosomal protein gene, and in about 25% of these cases, the RPS19 gene is the cause of this condition. The defect of this gene can disrupt the balance of blood cells, which appears as normocytic anemia, severe anemia, and macrocytic changes, along with a decrease in reticulocytes in the bone marrow. Patients need long-term corticosteroids. Whole exome sequencing of the blood sample of a patient with DBA was performed. The pathogenic mutation was investigated in the patient, his family and 30 people. The three-dimensional structure of the protein was evaluated using homology modeling and the interaction of the mutated protein with other proteins in the 40S ribosomal subunit. Peripheral blood test revealed a mutation on exon 3 of PRS19 gene (H42fs c.126-127 ins TA NM-00102) and chromosomal region 19q13.2. This mutation was autosomal dominant, during which amino acid number 42 of histidine was converted into a stop codon and a shortened protein was produced. The behavior of this protein with the PRS18 gene in healthy and mutated states shows that when the mutation occurs in PRS19, the amino acids Leu45, Ala46, Pro47, Tyr48, Asp49, Glu50 and Trp52, which are important residues connected are converted to RPS18, they are no longer present in this protein. Therefore, the binding of truncated RPS19 to RPS18 is significantly reduced. Although it seems that the presence of these residues may not prevent the interaction of RPS19 with RPS16 in the mutant state, it is possible that the mutant protein disrupts the spatial arrangement of other proteins and affects the interactions. affect them.

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