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| Status |
Public on Jan 01, 2015 |
| Title |
KLF1 null neonates display hydrops fetalis and a deranged erythroid transcriptome |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Third-party reanalysis
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| Summary |
We describe a case of severe neonatal anemia with kernicterus due to compound heterozygosity for null mutations in KLF1, each inherited from asymptomatic parents. One of the mutations is novel. This is the first described case of a KLF1 null human. The phenotype of severe DAT-negative non-spherocytic hemolytic anaemia (NSHA), jaundice, hepato-splenomegaly, and marked erythroblastosis is more severe than that present in CDA type IV due to dominant mutations in the second zinc-finger of KLF1. There was a very high level of HbF expression into childhood (>70%), consistent with a key role for KLF1 in human hemoglobin switching. We performed RNA-seq on circulating erythroblasts and found human KLF1 acts like mouse Klf1 to coordinate expression of many genes required to build a red cell including those encoding globins, cytoskeletal components, AHSP, heme synthesis enzymes, cell cycle regulators, and blood group antigens. We identify novel KLF1 target genes including KIF23 and KIF11 which are required for proper cytokinesis. We also identify new roles for KLF1 in autophagy, global transcriptional control and RNA splicing. We suggest loss of KLF1 should be considered in otherwise unexplained cases of severe neonatal NSHA or hydrops fetalis.
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| Overall design |
mRNA sequencing on peripheral blood from a family trio (mother, father and proband) where parents were asymptomatic and proband had severe neonatal anemia.
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| Contributor(s) |
Magor GW, Perkins AC |
| Citation(s) |
25724378 |
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| Submission date |
Aug 19, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Graham William Magor |
| E-mail(s) |
gmagor@mmri.mater.org.au
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| Organization name |
Mater Research
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| Lab |
Cancer Genomics
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| Street address |
37 Kent St
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| City |
Brisbane |
| State/province |
Queensland |
| ZIP/Postal code |
4152 |
| Country |
Australia |
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| Platforms (1) |
| GPL17303 |
Ion Torrent Proton (Homo sapiens) |
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| Samples (3) |
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| Relations |
| Reanalysis of |
GSM1297576 |
| Reanalysis of |
GSM1297581 |
| Reanalysis of |
GSM1297586 |
| Reanalysis of |
GSM1297577 |
| Reanalysis of |
GSM1297587 |
| Reanalysis of |
GSM1297582 |
| Reanalysis of |
GSM1297578 |
| Reanalysis of |
GSM1297583 |
| Reanalysis of |
GSM1297588 |
| Reanalysis of |
GSM1297579 |
| Reanalysis of |
GSM1297584 |
| Reanalysis of |
GSM1297589 |
| Reanalysis of |
GSM1297580 |
| Reanalysis of |
GSM1297585 |
| Reanalysis of |
GSM1297590 |
| BioProject |
PRJNA258589 |
| SRA |
SRP045664 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE60514_gene.matrix.txt.gz |
764.8 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Processed data are available on Series record |
| Raw data are available in SRA |
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