Genotype-degree of hemolysis correlation in hereditary spherocytosis.
Degree of hemolysis
Hereditary spherocytosis
Levitt’s carbon monoxide breath test
Next-generation sequencing
Red blood cell lifespan
Journal
BMC genomics
ISSN: 1471-2164
Titre abrégé: BMC Genomics
Pays: England
ID NLM: 100965258
Informations de publication
Date de publication:
06 Jun 2023
06 Jun 2023
Historique:
received:
18
02
2023
accepted:
06
05
2023
medline:
8
6
2023
pubmed:
7
6
2023
entrez:
6
6
2023
Statut:
epublish
Résumé
Hereditary spherocytosis (HS) is a common inherited hemolytic anemia, caused by mutations in five genes that encode erythrocyte membrane skeleton proteins. The red blood cell (RBC) lifespan could directly reflect the degree of hemolysis. In the present cohort of 23 patients with HS, we performed next-generation sequencing (NGS) and Levitt's carbon monoxide (CO) breath test to investigate the potential genotype-degree of hemolysis correlation. In the present cohort, we identified 8 ANK1,9 SPTB,5 SLC4A1 and 1 SPTA1 mutations in 23 patients with HS, and the median RBC lifespan was 14(8-48) days. The median RBC lifespan of patients with ANK1, SPTB and SLC4A1 mutations was 13 (8-23), 13 (8-48) and 14 (12-39) days, respectively, with no statistically significant difference (P = 0.618). The median RBC lifespan of patients with missense, splice and nonsense/insertion/deletion mutations was 16.5 (8-48), 14 (11-40) and 13 (8-20) days, respectively, with no significant difference (P = 0.514). Similarly, we found no significant difference in the RBC lifespan of patients with mutations located in the spectrin-binding domain and the nonspectrin-binding domain [14 (8-18) vs. 12.5 (8-48) days, P = 0.959]. In terms of the composition of mutated genes, 25% of patients with mild hemolysis carried ANK1 or SPTA1 mutations, while 75% of patients with mild hemolysis carried SPTB or SLC4A1 mutations. In contrast, 46.7% of patients with severe hemolysis had ANK1 or SPTA1 mutations and 53.3% of patients with severe hemolysis had SPTB or SLC4A1 mutations. However, there was no statistically significant difference in the distribution of mutated genes between the two groups (P = 0.400). The present study is the first to investigate the potential association between genotype and degree of hemolysis in HS. The present findings indicated that there is no significant correlation between genotype and degree of hemolysis in HS.
Sections du résumé
BACKGROUND
BACKGROUND
Hereditary spherocytosis (HS) is a common inherited hemolytic anemia, caused by mutations in five genes that encode erythrocyte membrane skeleton proteins. The red blood cell (RBC) lifespan could directly reflect the degree of hemolysis. In the present cohort of 23 patients with HS, we performed next-generation sequencing (NGS) and Levitt's carbon monoxide (CO) breath test to investigate the potential genotype-degree of hemolysis correlation.
RESULTS
RESULTS
In the present cohort, we identified 8 ANK1,9 SPTB,5 SLC4A1 and 1 SPTA1 mutations in 23 patients with HS, and the median RBC lifespan was 14(8-48) days. The median RBC lifespan of patients with ANK1, SPTB and SLC4A1 mutations was 13 (8-23), 13 (8-48) and 14 (12-39) days, respectively, with no statistically significant difference (P = 0.618). The median RBC lifespan of patients with missense, splice and nonsense/insertion/deletion mutations was 16.5 (8-48), 14 (11-40) and 13 (8-20) days, respectively, with no significant difference (P = 0.514). Similarly, we found no significant difference in the RBC lifespan of patients with mutations located in the spectrin-binding domain and the nonspectrin-binding domain [14 (8-18) vs. 12.5 (8-48) days, P = 0.959]. In terms of the composition of mutated genes, 25% of patients with mild hemolysis carried ANK1 or SPTA1 mutations, while 75% of patients with mild hemolysis carried SPTB or SLC4A1 mutations. In contrast, 46.7% of patients with severe hemolysis had ANK1 or SPTA1 mutations and 53.3% of patients with severe hemolysis had SPTB or SLC4A1 mutations. However, there was no statistically significant difference in the distribution of mutated genes between the two groups (P = 0.400).
CONCLUSION
CONCLUSIONS
The present study is the first to investigate the potential association between genotype and degree of hemolysis in HS. The present findings indicated that there is no significant correlation between genotype and degree of hemolysis in HS.
Identifiants
pubmed: 37280519
doi: 10.1186/s12864-023-09364-8
pii: 10.1186/s12864-023-09364-8
pmc: PMC10245416
doi:
Substances chimiques
Ankyrins
0
Spectrin
12634-43-4
Cytoskeletal Proteins
0
Membrane Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
304Informations de copyright
© 2023. The Author(s).
Références
Am J Hematol. 2021 Oct 1;96(10):1232-1240
pubmed: 34265098
J Biol Chem. 2013 Sep 13;288(37):26372-84
pubmed: 23846695
Blood Cells Mol Dis. 2005 Nov-Dec;35(3):345-7
pubmed: 16223590
Br J Haematol. 2020 Nov;191(3):486-496
pubmed: 32436265
J Mol Biol. 2012 Apr 6;417(4):336-50
pubmed: 22310050
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
Zhonghua Xue Ye Xue Za Zhi. 2019 May 14;40(5):447-448
pubmed: 31207716
Lancet. 2008 Oct 18;372(9647):1411-26
pubmed: 18940465
Blood. 2016 Jan 14;127(2):187-99
pubmed: 26537302
Clin Genet. 2016 Jul;90(1):69-78
pubmed: 26830532
Front Genet. 2020 Aug 18;11:953
pubmed: 33014018
J Mol Biol. 2013 Jul 24;425(14):2591-608
pubmed: 23583773
J Biol Chem. 1996 Jun 28;271(26):15695-702
pubmed: 8663089
Neurobiol Aging. 2019 Feb;74:70-76
pubmed: 30439595
Br J Haematol. 2012 Jan;156(1):37-49
pubmed: 22055020
Front Genet. 2021 Mar 18;12:652376
pubmed: 33868383
Zhonghua Xue Ye Xue Za Zhi. 2015 Jul;36(7):598-601
pubmed: 26304086
J Cell Mol Med. 2009 Nov-Dec;13(11-12):4364-76
pubmed: 19840192
Proc Natl Acad Sci U S A. 2012 Mar 27;109(13):4822-7
pubmed: 22411828
Hemasphere. 2019 Aug 07;3(4):e276
pubmed: 31723846