Alternative titles; symbols
HGNC Approved Gene Symbol: KRT85
Cytogenetic location: 12q13.13 Genomic coordinates (GRCh38): 12:52,360,006-52,367,481 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 12q13.13 | Ectodermal dysplasia 4, hair/nail type | 602032 | Autosomal recessive | 3 |
See KRTHA1 (601077) for general information on hair keratins.
By screening a human scalp cDNA library with a mouse genomic sequence encoding the conserved N-terminal region of Hb4 (see 602766), Rogers et al. (1997) isolated a cDNA encoding KRTHB5, or HB5. The predicted protein has 507 amino acids. The amino acid sequences of HB1 (602153), HB3 (602765), HB5, and HB6 (601928) are extremely conserved in the alpha-helical, N-terminal, and proximal C-terminal domains. In situ hybridization studies demonstrated that type II keratin genes are sequentially activated in the hair follicle in the following order: HB5--(HB1, HB3)--HB6. The onset of HB5 mRNA synthesis occurs immediately above a small population of matrix cells at the base of the hair bulb and in the trichocytes lining the dermal papilla. Synthesis extends upward through the matrix and ends in the lower part of the hair shaft cortex. The authors noted that the mRNA expression patterns of HB5 and HA5 (602764) are nearly identical.
In a large consanguineous Pakistani family with 'pure' ectodermal dysplasia of the hair and nails (ECTD4; 602032) that had been mapped to a 15.0-Mb region on chromosome 12q13.13, Naeem et al. (2006) sequenced 6 candidate type II hair keratin genes and identified homozygosity for a missense mutation in the KRTHB5 gene (602767.0001) in all affected individuals.
In 2 consanguineous Pakistani families with autosomal recessive hair and nail ectodermal dysplasia linked to chromosome 12, Shimomura et al. (2010) identified homozygous mutations in the KRT85 gene (602767.0001-602767.0002).
In affected members of a large consanguineous Pakistani family with 'pure' ectodermal dysplasia of the hair and nails (ECTD4; 602032), Naeem et al. (2006) identified homozygosity for a 233G-A transition in exon 1 of the KRTHB5 gene, resulting in an arg78-to-his (R78H) substitution. The authors noted that arginine-78 is highly conserved in the head domains of type II keratins in mouse, human, and sheep. The mutation was present in heterozygosity in obligate carriers within the family and was not found in 200 chromosomes from Pakistani controls.
In affected members of a consanguineous Pakistani family (family B) with hair and nail ectodermal dysplasia, Shimomura et al. (2010) identified homozygosity for the R78H mutation. Affected individuals had complete alopecia and diffuse follicular papules on the scalp. Facial and body hair was absent, and nails showed severe deformities.
In affected members of a consanguineous Pakistani family (family B) with ectodermal dysplasia of the hair and nails (ECTD4; 602032), Shimomura et al. (2010) identified homozygosity for a 2-bp deletion (1448_1449delCT) in exon 9 of the KRT85 gene. The mutation was predicted to result in a frameshift at codon 483 and a premature stop codon 18 amino acids downstream of the mutation (Pro483ArgfsTer18). Affected members had sparse, brittle hair and diffuse follicular papules on the scalp. The scalp hair shaft showed varying degrees of thickness. Facial and body hair was less dense overall, and the distal ends of the nails were irregularly shaped and broke easily. The mutation segregated with the disorder in the family and was not found in 100 Pakistani control individuals.
Naeem, M., Wajid, M., Lee, K., Leal, S. M., Ahmad, W. A mutation in the hair matrix and cuticle keratin KRTHB5 gene causes ectodermal dysplasia of hair and nail type. (Letter) J. Med. Genet. 43: 274-279, 2006. [PubMed: 16525032] [Full Text: https://doi.org/10.1136/jmg.2005.033381]
Rogers, M. A., Langbein, L., Praetzel, S., Moll, I., Krieg, T., Winter, H., Schweizer, J. Sequences and differential expression of three novel human type-II hair keratins. Differentiation 61: 187-194, 1997. [PubMed: 9084137] [Full Text: https://doi.org/10.1046/j.1432-0436.1997.6130187.x]
Shimomura, T., Wajid, M., Kurban, M., Sato, N., Christiano, A. M. Mutations in the keratin 85 (KRT86/hHb5) gene underlie pure hair and nail ectodermal dysplasia. (Letter) J. Invest. Derm. 130: 892-895, 2010. [PubMed: 19865094] [Full Text: https://doi.org/10.1038/jid.2009.341]