Whole-exome sequencing uncovered genetic diagnosis of severe inherited haemolytic anaemia: Correlation with clinical phenotypes
Issued Date
2022-09-01
Resource Type
ISSN
00071048
eISSN
13652141
Scopus ID
2-s2.0-85133800490
Pubmed ID
35819869
Journal Title
British Journal of Haematology
Volume
198
Issue
6
Start Page
1051
End Page
1064
Rights Holder(s)
SCOPUS
Bibliographic Citation
British Journal of Haematology Vol.198 No.6 (2022) , 1051-1064
Suggested Citation
Songdej D., Kadegasem P., Tangbubpha N., Sasanakul W., Deelertthaweesap B., Chuansumrit A., Sirachainan N. Whole-exome sequencing uncovered genetic diagnosis of severe inherited haemolytic anaemia: Correlation with clinical phenotypes. British Journal of Haematology Vol.198 No.6 (2022) , 1051-1064. 1064. doi:10.1111/bjh.18356 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/85603
Title
Whole-exome sequencing uncovered genetic diagnosis of severe inherited haemolytic anaemia: Correlation with clinical phenotypes
Author's Affiliation
Other Contributor(s)
Abstract
Next-generation sequencing has shed light on the diagnosis of previously unsolved cases of inherited haemolytic anaemia (IHA). We employed whole-exome sequencing to explore the molecular diagnostic spectrum of 21 unrelated Thai paediatric patients with non-thalassemic IHA, presenting hydrops fetalis and/or becoming transfusion-dependent for 1 year or more or throughout their lifespan. Anaemia was detected prenatally, within the first month and the fifth year of life in three, 12 and six patients respectively. Molecular diagnosis obtained from all patients revealed SPTB as the most frequently mutated gene (four reported, three novel), found in 31 of 42 studied alleles. The other two mutated genes identified were ANK1 (three novel) and KLF1 (two reported). Four recurring mutations within exon 29/30 (NM_001024858.2) accounted for the vast majority (90%) of mutated SPTB alleles, biallelic inheritance of which resulted in the most severe phenotypes: hydrops fetalis and life-long transfusion dependency. Dominant ANK1 (n = 3) and SPTB (n = 2) mutations and biallelic class 2 KLF1 mutations (n = 1) led to a shorter period of transfusion dependency. Our study demonstrated that mutated SPTB causing red-cell membranopathy is likely the most common cause of severe non-thalassemic IHA among Thai patients. This urges carrier screening in the population to prevent subsequent, severely affected births.