Alternative titles; symbols
HGNC Approved Gene Symbol: CYP4F22
Cytogenetic location: 19p13.12 Genomic coordinates (GRCh38) : 19:15,508,525-15,552,317 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 19p13.12 | Ichthyosis, congenital, autosomal recessive 5 | 604777 | Autosomal recessive | 3 |
By database analysis, followed by RT-PCR, Lefevre et al. (2006) cloned CYP4F22, which encodes a 531-amino acid protein with a calculated molecular mass of about 62 kD. CYP4F22 is evolutionarily conserved, displays 86% protein homology with rodent orthologs, and exhibits 67% amino acid homology with CYP4F2 (604426) and CYP4F3 (601270), which are also located in the F subfamily gene cluster on chromosome 19. RT-PCR analysis of human tissues detected high expression in culture keratinocytes and testis with lower expression in placenta, bone marrow, small intestine, liver, skeletal muscle, brain, and kidney.
Lefevre et al. (2006) determined that the CYP4F22 gene contains 12 exons.
Lefevre et al. (2006) noted that the CYP4F22 gene maps to chromosome 19p13.12.
By linkage analysis of 12 consanguineous families with autosomal recessive congenital ichthyosis of the lamellar type (ARCI5; 604777), Lefevre et al. (2006) mapped the disease locus to a 3-Mb region on chromosome 19 (lod = 15.83 at D19S930, theta = 0.0). Lefevre et al. (2006) identified 7 different mutations in the CYP4F22 gene (see, e.g., 611495.0001-611495.0004) in the 12 consanguineous families. There were 5 missense mutations and 2 deletions. The phenotype usually presented as lamellar ichthyosis and hyperlinearity of palms and soles. The authors hypothesized that CYP4F22 plays a role in the 12(R)-lipoxygenase pathway that has been implicated in Sjogren-Larsson syndrome (270200) and in congenital ichthyosis (612281) due to mutation in the NIPAL4 gene (609383).
In 4 affected individuals from a large consanguineous Israeli Druze family with ARCI, Lugassy et al. (2008) identified homozygosity for a nonsense mutation in the CYP4F22 gene (W521X; 611495.0005).
In 1 French and 5 Algerian consanguineous families with autosomal recessive congenital ichthyosis (ARCI5; 604777) of the lamellar type, Lefevre et al. (2006) identified homozygosity for a 1303C-T transition in exon 10 of the CYP4F22 gene, resulting in a his435-to-tyr (H435Y) substitution in a highly conserved region of the protein.
In a consanguineous Algerian family with autosomal recessive congenital ichthyosis (ARCI5; 604777) of the lamellar type, Lefevre et al. (2006) identified homozygosity for a 1306C-G transversion in exon 10 of the CYP4F22 gene, resulting in a his436-to-asp (H436D) substitution in a highly conserved region of the protein.
In a consanguineous Algerian family with autosomal recessive congenital ichthyosis (ARCI5; 604777) of the lamellar type, Lefevre et al. (2006) identified homozygosity for a 728G-A transition in exon 6 of the CYP4F22 gene, resulting in an arg243-to-his (R243H) substitution in a highly conserved region of the protein.
In a consanguineous Italian family with autosomal recessive congenital ichthyosis (ARCI5; 604777) of the lamellar type, Lefevre et al. (2006) identified homozygosity for a large genomic deletion of exons 3 to 12 of the CYP4F22 gene.
In 4 affected individuals from a large consanguineous Israeli Druze family with autosomal recessive congenital ichthyosis (ARCI5; 604777), Lugassy et al. (2008) identified homozygosity for a 1563G-A transition in the CYP4F22 gene, predicted to result in a trp521-to-ter (W521X) substitution. The mutation segregated with disease in the family and was not found in 50 controls.
Lefevre, C., Bouadjar, B., Ferrand, V., Tadini, G., Megarbane, A., Lathrop, M., Prud'homme, J.-F., Fischer, J. Mutations in a new cytochrome P450 gene in lamellar ichthyosis type 3. Hum. Molec. Genet. 15: 767-776, 2006. [PubMed: 16436457] [Full Text: https://doi.org/10.1093/hmg/ddi491]
Lugassy, J., Hennies, H. C., Indelman, M., Khamaysi, Z., Bergman, R., Sprecher, E. Rapid detection of homozygous mutations in congenital recessive ichthyosis. Arch. Derm. Res. 300: 81-85, 2008. [PubMed: 18034255] [Full Text: https://doi.org/10.1007/s00403-007-0815-0]