OMIA:002109-9913 : Tricho-dento-osseous-like syndrome in Bos taurus
Categories: Integument (skin) phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 190320 (trait) , 600525 (gene)
Links to MONDO diseases:
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal dominant
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2017
Species-specific description: In a remarkable indication of the power of modern genomic tools, Hofstetter et al. (2017) reported a novel form of curly coat in a single Brown Swiss calf, the offspring of two normal-coated parents. By whole-genome sequencing of the calf and its sire and dam, followed by informed interrogation of the sequence data (as described below), these authors were able to identify a likely causal variant in a gene which, when mutated in humans, gives rise to a similar phenotype. Thus was a new animal model of a human disorder identified (see "Possible human homologue" above)
Inheritance: As reported by Hofstetter et al. (2017), the absence of the variant in both parents strongly suggests that the variant is a de novo dominant mutation. And the mutated gene, DLX3, is located on chromosome BTA19. Hence, even without pedigree data, it is reasonable to conclude that the trait is autosomal dominant.
Molecular basis: Hofstetter et al. (2017): "Genome-wide filtering for sequence variants in the whole genome that were present heterozygous only in the affected calf and homozygous wild-type (WT) in the genomes of both parents, resulted in 276 variants representing putative de novo sequence variants (Table S1). Out of these 276 variants, only a single 10 bp insertion on chromosome 19 (g.37298375_37298376insGGAGCACAGG) was located in a protein coding gene, namely in exon 3 of the bovine distal-less homeobox gene (DLX3) leading to a frameshift. . . . The mutation was predicted to produce a frameshift downstream the homeobox encoding region of the DLX3 mRNA (NM_001081622: c.584_585insGGAGCACAGG; NP_001075091: p.Ser198ArgfsTer99) resulting in a mutant protein of 296 residues. In comparison to the normal 287 amino acid-long DLX3 protein, the C-terminal transactivation domain of the WT protein is replaced by a 99 peptide with no similarities to known proteins".
Clinical features: Hofstetter et al. (2017): "Examination revealed a dull tousled hair coat with mild hypotrichosis of the ventral neck and legs (Figure 1a,b). The coat colour was typical for this breed. The hair shafts were not obviously fragile. The eyelashes were curly on both sides (Figure 1c). The concave and convex aspects of the pinnae were hypotrichotic (Figure 1d). The skin was dry and covered with fine scale. The incisor teeth were erupted and aligned correctly, and had a slight brown discolouration (Figure S1). Trichograms demonstrated irregular shaped hair shafts characterized by multiple indentations of the cuticle, cortex and medulla (Figure S2). Clinical examination was otherwise unremarkable. A complete blood count and biochemical analysis was unremarkable."
Pathology: Hofstetter et al. (2017): "Histological examination of skin biopsies demonstrated follicular dysplasia characterized by large vacuoles within the Henle and Huxley layer of the suprabulbar region of the hair follicles, an irregular thickness of the cornified inner root sheath and severely irregular contour of the hair shafts"
Breed: Brown Swiss (Cattle) (VBO_0000166).
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|DLX3||distal-less homeobox 3||Bos taurus||19||NC_037346.1 (36662426..36667620)||DLX3||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|615||Brown Swiss (Cattle)||Tricho-dento-osseous-like syndrome||DLX3||insertion, small (<=20)||Naturally occurring variant||ARS-UCD1.2||19||g.36665831_36665832insGGAGCACA||c.584_585insGGAGCACAGG||p.(S198Rfs*99)||NM_001081622 position is g.37298375_37298376insGGAGCACA||2017||28670783||The genomic location on ARS-UCD1.2 was determined by Katie Eager and Shernae Woolley, EMAI, NSW. Department of Primary Industries.|
|2017||Hofstetter, S., Welle, M., Gorgas, D., Balmer, P., Roosje, P., Mock, T., Meylan, M., Jagannathan, V., Drögemüller, C. :|
|A de novo germline mutation of DLX3 in a Brown Swiss calf with tricho-dento-osseus-like syndrome. Vet Dermatol :, 2017. Pubmed reference: 28670783 . DOI: 10.1111/vde.12462.|
- Changed by Frank Nicholas on 05 Jul 2017
- Created by Frank Nicholas on 05 Jul 2017