Molecular insights into hereditary elliptocytosis and pyropoikilocytosis: NGS uncovers multiple potential candidate genes.

Autor: Shome DK; Department of Pathology, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain. dr.dkshome@gmail.com.; Education & Proficiency Center, King Hamad University Hospital, Manama, Kingdom of Bahrain. dr.dkshome@gmail.com., Das P; Education & Proficiency Center, King Hamad University Hospital, Manama, Kingdom of Bahrain. priyadas001@gmail.com., Akbar GA; Department of Pathology, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain., Taha S; Princess Al-Jawhara Centre for Molecular Medicine, Genetics and Inherited Diseases, Arabian Gulf University, Manama, Kingdom of Bahrain., Radhi A; Department of Pathology, Salmaniya Medical Complex, Manama, Kingdom of Bahrain., Al-Saad K; Department of Pediatrics, Salmaniya Medical Complex, Manama, Kingdom of Bahrain., Helmy R; Department of Pathology, Blood Bank and Laboratory Medicine, King Hamad University Hospital, Manama, Kingdom of Bahrain.
Jazyk: angličtina
Zdroj: Annals of hematology [Ann Hematol] 2023 Sep; Vol. 102 (9), pp. 2343-2351. Date of Electronic Publication: 2023 Jul 04.
DOI: 10.1007/s00277-023-05337-9
Abstrakt: Hereditary elliptocytosis (HE) and pyropoikilocytosis (HPP) are considered a group of hemolytic anemias (HE/HPP) due to inherited abnormalities of erythrocyte membrane proteins with a worldwide distribution. Most cases are associated with molecular abnormalities linked to spectrin, band 4.1, and ankyrin. The present study aimed to identify significant molecular signatures on a target panel of 8 genes using whole exome sequencing (WES) in 9 Bahraini patients with elliptocytosis. Case selection was based on presence of anemia not associated with iron deficiency or hemoglobinopathy and demonstrating > 50% elliptocytes in blood smears. The c.779 T > C mutation of SPTA1 (Spectrin alpha), which is a known deleterious missense mutation that inhibits normal association of spectrin molecules to form tetramers, was seen in 4 patients in homozygous (n = 1) and heterozygous (n = 3) states. The αLELY abnormality in association with compound heterozygous mutations in SPTA1 was present in 5 patients (2 associated with the SPTA1 c.779 T > C variant; 3 with c.3487 T > G and various other SPTA1 mutations of uncertain/unknown significance). Seven patients had SPTB (Spectrin beta) mutations, predicted as likely benign by in silico analysis. A novel EPB41 (Erythrocyte Membrane Protein Band 4.1) mutation with potential deleterious impact was also seen. Finally, 2 cases showed an InDel (insertion-deletion mutations) abnormality in the gene that codes for the mechanosensitive ion-channel PIEZO (Piezo Type Mechanosensitive Ion Channel Component 1). PIEZO mutations are reported to cause red cell dehydration but have not been previously described in HE/HPP. Results of this study confirm the involvement of previously reported abnormalities in SPTA1 and suggest possible involvement of other candidate genes in a disorder involving polygenic interactions.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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