Molecular insights into hereditary elliptocytosis and pyropoikilocytosis: NGS uncovers multiple potential candidate genes.
Hemolytic anemia
Hereditary elliptocytosis
Pyropoikilocytosis
RBC dehydration
Journal
Annals of hematology
ISSN: 1432-0584
Titre abrégé: Ann Hematol
Pays: Germany
ID NLM: 9107334
Informations de publication
Date de publication:
Sep 2023
Sep 2023
Historique:
received:
16
03
2023
accepted:
20
06
2023
medline:
23
8
2023
pubmed:
4
7
2023
entrez:
3
7
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37400730
doi: 10.1007/s00277-023-05337-9
pii: 10.1007/s00277-023-05337-9
doi:
Substances chimiques
Spectrin
12634-43-4
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2343-2351Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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