Homozygous mutations in a predicted endonuclease are a novel cause of congenital dyserythropoietic anemia type I.
The congenital dyserythropoietic anemias are a heterogeneous group of rare disorders primarily affecting erythropoiesis with characteristic morphological abnormalities and a block in erythroid maturation. Mutations in the CDAN1 gene, which encodes Codanin-1, underlie the majority of congenital dyser...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2013
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| _version_ | 1797073987002433536 |
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| author | Babbs, C Roberts, N Sanchez-Pulido, L McGowan, S Ahmed, MR Brown, J Sabry, M Bentley, DR Mcvean, G Donnelly, P Gileadi, O Ponting, C Higgs, D Buckle, V |
| author_facet | Babbs, C Roberts, N Sanchez-Pulido, L McGowan, S Ahmed, MR Brown, J Sabry, M Bentley, DR Mcvean, G Donnelly, P Gileadi, O Ponting, C Higgs, D Buckle, V |
| author_sort | Babbs, C |
| collection | OXFORD |
| description | The congenital dyserythropoietic anemias are a heterogeneous group of rare disorders primarily affecting erythropoiesis with characteristic morphological abnormalities and a block in erythroid maturation. Mutations in the CDAN1 gene, which encodes Codanin-1, underlie the majority of congenital dyserythropoietic anemia type I cases. However, no likely pathogenic CDAN1 mutation has been detected in approximately 20% of cases, suggesting the presence of at least one other locus. We used whole genome sequencing and segregation analysis to identify a homozygous T to A transversion (c.533T>A), predicted to lead to a p.L178Q missense substitution in C15ORF41, a gene of unknown function, in a consanguineous pedigree of Middle-Eastern origin. Sequencing C15ORF41 in other CDAN1 mutation-negative congenital dyserythropoietic anemia type I pedigrees identified a homozygous transition (c.281A>G), predicted to lead to a p.Y94C substitution, in two further pedigrees of SouthEast Asian origin. The haplotype surrounding the c.281A>G change suggests a founder effect for this mutation in Pakistan. Detailed sequence similarity searches indicate that C15ORF41 encodes a novel restriction endonuclease that is a member of the Holliday junction resolvase family of proteins. |
| first_indexed | 2024-03-06T23:29:49Z |
| format | Journal article |
| id | oxford-uuid:6ba4ffd9-72ce-41a0-8530-7d0694960678 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:29:49Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:6ba4ffd9-72ce-41a0-8530-7d06949606782022-03-26T19:05:24ZHomozygous mutations in a predicted endonuclease are a novel cause of congenital dyserythropoietic anemia type I.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6ba4ffd9-72ce-41a0-8530-7d0694960678EnglishSymplectic Elements at Oxford2013Babbs, CRoberts, NSanchez-Pulido, LMcGowan, SAhmed, MRBrown, JSabry, MBentley, DRMcvean, GDonnelly, PGileadi, OPonting, CHiggs, DBuckle, VThe congenital dyserythropoietic anemias are a heterogeneous group of rare disorders primarily affecting erythropoiesis with characteristic morphological abnormalities and a block in erythroid maturation. Mutations in the CDAN1 gene, which encodes Codanin-1, underlie the majority of congenital dyserythropoietic anemia type I cases. However, no likely pathogenic CDAN1 mutation has been detected in approximately 20% of cases, suggesting the presence of at least one other locus. We used whole genome sequencing and segregation analysis to identify a homozygous T to A transversion (c.533T>A), predicted to lead to a p.L178Q missense substitution in C15ORF41, a gene of unknown function, in a consanguineous pedigree of Middle-Eastern origin. Sequencing C15ORF41 in other CDAN1 mutation-negative congenital dyserythropoietic anemia type I pedigrees identified a homozygous transition (c.281A>G), predicted to lead to a p.Y94C substitution, in two further pedigrees of SouthEast Asian origin. The haplotype surrounding the c.281A>G change suggests a founder effect for this mutation in Pakistan. Detailed sequence similarity searches indicate that C15ORF41 encodes a novel restriction endonuclease that is a member of the Holliday junction resolvase family of proteins. |
| spellingShingle | Babbs, C Roberts, N Sanchez-Pulido, L McGowan, S Ahmed, MR Brown, J Sabry, M Bentley, DR Mcvean, G Donnelly, P Gileadi, O Ponting, C Higgs, D Buckle, V Homozygous mutations in a predicted endonuclease are a novel cause of congenital dyserythropoietic anemia type I. |
| title | Homozygous mutations in a predicted endonuclease are a novel cause of congenital dyserythropoietic anemia type I. |
| title_full | Homozygous mutations in a predicted endonuclease are a novel cause of congenital dyserythropoietic anemia type I. |
| title_fullStr | Homozygous mutations in a predicted endonuclease are a novel cause of congenital dyserythropoietic anemia type I. |
| title_full_unstemmed | Homozygous mutations in a predicted endonuclease are a novel cause of congenital dyserythropoietic anemia type I. |
| title_short | Homozygous mutations in a predicted endonuclease are a novel cause of congenital dyserythropoietic anemia type I. |
| title_sort | homozygous mutations in a predicted endonuclease are a novel cause of congenital dyserythropoietic anemia type i |
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