Alternative titles; symbols
HGNC Approved Gene Symbol: CDIN1
Cytogenetic location: 15q14 Genomic coordinates (GRCh38): 15:36,579,626-36,810,244 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 15q14 | Dyserythropoietic anemia, congenital, type Ib | 615631 | Autosomal recessive | 3 |
By RT-PCR of total RNA from transformed B lymphocytes and cultured normal human erythroblasts, Babbs et al. (2013) cloned human C15ORF41. The deduced 281-amino acid protein has 2 helix-turn-helix domains in its N-terminal half and a nuclease domain in its C-terminal half. Global gene expression analysis showed that C15ORF41 was uniformly expressed during erythroid differentiation. Expression array analysis revealed that C15ORF41 was widely expressed, with elevated expression in B lymphoblasts, CD34 (142230)-positive cells, cardiomyocytes, and fetal liver, suggesting a specific requirement in hematopoiesis. Database analysis revealed conservation of C15ORF41 in eukaryotes, with possible orthologs in archaea and viruses.
Babbs et al. (2013) determined that the C15ORF41 gene contains 11 exons and spans over 227.8 kb.
Babbs et al. (2013) reported that the C15ORF41 gene maps to chromosome 15q14.
In affected members of 3 unrelated consanguineous families with congenital dyserythropoietic anemia type Ib (CDAN1B; 615631), Babbs et al. (2013) identified 2 different homozygous missense mutations in the C15ORF41 gene (L178Q, 615626.0001 and Y94C, 615626.0002). The mutation in the first family was found by whole-genome sequencing, whereas the mutation in the other 2 families was found by direct sequencing of the C15ORF41 gene in 9 probands with the disorder. Functional studies of the mutations were not performed.
In 3 affected sibs, born of consanguineous Kuwaiti parents, with severe congenital dyserythropoietic anemia type Ib (CDAN1B; 615631), Babbs et al. (2013) identified a homozygous c.533T-A transversion in exon 8 of the C15ORF41 gene, resulting in a leu178-to-gln (L178Q) substitution at a highly conserved residue in a hydrophobic core domain. The mutation, which was found by whole-genome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not present in the dbSNP (build 136) or Exome Variant Server databases, or in 41 ethnically matched controls. Functional studies of the variant were not performed. The family had previously been reported by Sabry et al. (1997).
In affected members of 2 unrelated consanguineous Pakistani families with CDAN1B (615631), Babbs et al. (2013) identified a homozygous c.281A-G transition in exon 5 of the C15ORF41 gene, resulting in a tyr94-to-cys (Y94C) substitution in a hydrophobic core domain. Haplotype analysis indicated a founder effect. Although the residue is not very highly conserved, the introduction of a cysteine could form covalent bonds, thus disrupting tertiary structure of the protein. The mutation was found by direct sequencing of the C15ORF41 gene in 9 probands with CDA type I. It was not found in the dbSNP (build 136) or Exome Variant Server databases. One of the families had previously been reported by Ahmed et al. (2006). Functional studies of the variant were not performed.
Ahmed, M. R., Zaki, M., Sabry, M. A., Higgs, D., Vyas, P., Wood, W., Wickramasinghe, S. N. Evidence of genetic heterogeneity in congenital dyserythropoietic anaemia type I. (Letter) Brit. J. Haemat. 133: 444-445, 2006. [PubMed: 16643456] [Full Text: https://doi.org/10.1111/j.1365-2141.2006.06089.x]
Babbs, C., Roberts, N. A., Sanchez-Pulido, L., McGowan, S. J., Ahmed, M. R., Brown, J. M., Sabry, M. A., WGS500 Consortium, Bentley, D. R., McVean, G. A., Donnelly, P., Gileadi, O., Ponting, C. P., Higgs, D. R., Buckle, V. J. Homozygous mutations in a predicted endonuclease are a novel cause of congenital dyserythropoietic anemia type I. Haematologica 98: 1383-1387, 2013. [PubMed: 23716552] [Full Text: https://doi.org/10.3324/haematol.2013.089490]
Sabry, M. A., Zaki, M., al Awadi, S. A., al Saleh, Q., Mattar, M. S. Non-haematological traits associated with congenital dyserythropoietic anaemia type 1: a new entity emerging. Clin. Dysmorph. 6: 205-212, 1997. [PubMed: 9220189] [Full Text: https://doi.org/10.1097/00019605-199707000-00002]