HGNC Approved Gene Symbol: TUFT1
Cytogenetic location: 1q21.3 Genomic coordinates (GRCh38): 1:151,540,309-151,583,583 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 1q21.3 | Woolly hair-skin fragility syndrome | 620415 | Autosomal recessive | 3 |
Tuftelin is an acidic protein found in developing and mature extracellular enamel, the unique and highly mineralized ectodermal tissue covering vertebrate teeth (Deutsch, 1989; Deutsch et al., 1991). It is thought to play a major role in mineralization and structural organization of enamel.
Deutsch et al. (1992) cloned and sequenced 4 exons of the tuftelin gene from a human genomic library. MacDougall et al. (1998) described the cloning, characterization, and tissue expression pattern of mouse tuftelin cDNA. Bashir et al. (1998) cloned the bovine tuftelin gene. They commented that the protein does not appear to share homology or domain motifs with any other known protein. They also isolated the 3-prime portion of the human gene and demonstrated agreement between the bovine and human sequences in the segment studied. Differences between the sequence they reported and that reported by Deutsch et al. (1991) suggested the possibility of an unusual type of polymorphism that would result in markedly different amino acid sequences at the C-terminal region of the protein.
Jackson et al. (2023) interrogated scRNASeq data from the Human Protein Atlas and observed enriched expression of TUFT1 in basal and suprabasal keratinocytes. In addition, scRNASeq data using adult mouse full-thickness skin showed Tuft1 expression in keratinocytes and the dermal sheath.
By fluorescence in situ hybridization, Deutsch et al. (1994) mapped the TUFT1 gene to chromosome 1q21-q31. They raised the possibility that an autosomal dominant form of amelogenesis imperfecta (104500, 104530) is due to a mutation in this gene. By FISH, Bashir et al. (1998) localized the TUFT1 gene to chromosome 1q21.
In 9 affected individuals from 3 families with woolly hair and skin fragility (WHSF; 620415), Jackson et al. (2023) identified homozygosity for mutations in the TUFT1 gene: a Pakistani sister and brother were homozygous for a 1-bp deletion (600087.0001), and affected individuals from 2 families of Irish ancestry were homozygous for the same splice site mutation (600087.0002). The mutations segregated with disease in each family, and were either not found or present at low minor allele frequency, only in heterozygosity, in public variant databases.
In a Pakistani sister and brother (family 1) with woolly hair and skin fragility (WHSF; 620415), Jackson et al. (2023) identified homozygosity for a 1-bp deletion (c.563delG, NM_020127) in exon 7 of the TUFT1 gene, causing a frameshift predicted to result in a premature termination codon (Gln189AsnfsTer49). The deletion was present in heterozygosity in their unaffected first-cousin parents. Immunolabeling showed markedly reduced immunoreactivity for tuftelin-1 in patient skin compared to control.
In 4 sibs of Irish Traveller ancestry and their female cousin (family 2), as well as a sister and brother of Irish ancestry (family 3), who had skin fragility, keratosis pilaris, and woolly hair (WHSF; 620415), Jackson et al. (2023) identified homozygosity for a splice site mutation (c.60+1G-A, NM_020127) in intron 1 of the TUFT1 gene. The mutation segregated with disease in both families, and was present in only 3 individuals in the gnomAD database, all heterozygotes. Haplotype analysis suggested that the most recent common ancestor for variant carriers in the 2 families lived between 18.6 and 21.6 generations previously. Immunolabeling showed markedly reduced immunoreactivity for tuftelin-1 in patient skin compared to control.
Bashir, M. M., Abrams, W. R., Tucker, T., Sellinger, B., Budarf, M., Emanuel, B., Rosenbloom, J. Molecular cloning and characterization of the bovine and human tuftelin genes. Connect. Tissue Res. 39: 13-24, 1998. [PubMed: 11062985] [Full Text: https://doi.org/10.3109/03008209809023908]
Deutsch, D., Palmon, A., Dafni, L., Fisher, L., Termine, J. D., Young, M. Cloning, sequencing, and characterization of tuftelin: a novel acidic enamel protein. Connect. Tissue Res. 27: 121 only, 1992.
Deutsch, D., Palmon, A., Fisher, L. W., Kolodny, N., Termine, J. D., Young, M. F. Sequencing of bovine enamelin (tuftelin), a novel acidic enamel protein. J. Biol. Chem. 266: 16021-16028, 1991. [PubMed: 1874744]
Deutsch, D., Palmon, A., Young, M. F., Selig, S., Kearns, W. G., Fisher, L. W. Mapping of the human tuftelin (TUFT1) gene to chromosome 1 by fluorescence in situ hybridization. (Abstract) Mammalian Genome 5: 461-462, 1994.
Deutsch, D. Structure and function of enamel gene products. Anat. Rec. 224: 189-210, 1989. [PubMed: 2672884] [Full Text: https://doi.org/10.1002/ar.1092240209]
Jackson, A., Moss, C., Chandler, K. E., Balboa, P. L., Bageta, M. L., Petrof, G., Martinez, A. E., Liu, L., Guy, A., Mellerio, J. E., Lee, J. Y. W., Ogboli, M., Ryan, G., Genomics England Research Consortium, McGrath, J. A., Banka, S. Biallelic TUFT1 variants cause woolly hair, superficial skin fragility and desmosomal defects. Brit. J. Derm. 188: 75-83, 2023. [PubMed: 36689522] [Full Text: https://doi.org/10.1093/bjd/ljac026]
MacDougall, M., Simmons, D., Dodds, A., Knight, C., Luan, X., Zeichner-David, M., Zhang, C., Ryu, O. H., Qian, Q., Simmer, J. P., Hu, C.-C. Cloning, characterization, and tissue expression pattern of mouse tuftelin cDNA. J. Dent. Res. 77: 1970-1978, 1998. [PubMed: 9839784] [Full Text: https://doi.org/10.1177/00220345980770120401]