Tricho-dento-osseous-like syndrome

Phene ID

4032

Name

Tricho-dento-osseous-like syndrome

Phene Name

N/A

OMIA ID

2109

Species ID

9913

Characterised

Yes

Characterised Year

2017

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)

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.

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".