Sonja Hofstetter1, Monika Welle2,3, Daniela Gorgas4, Pierre Balmer3,5, Petra Roosje3,5, Thomas Mock6, Mireille Meylan6, Vidhya Jagannathan1, Cord Drögemüller1. 1. Vetsuisse Faculty, Institute of Genetics, University of Bern, Bremgartenstrasse 109a, Bern, 3001, Switzerland. 2. Vetsuisse Faculty, Institute of Animal Pathology, University of Bern, Länggassstrasse 122, Bern, 3001, Switzerland. 3. DermFocus, University of Bern, Bremgartenstrasse 109a, Bern, 3001, Switzerland. 4. Vetsuisse Faculty, Division of Radiology, Department of Clinical Veterinary Medicine, University of Bern, Länggassstrasse 128, Bern, 3001, Switzerland. 5. Vetsuisse Faculty, Division of Clinical Dermatology, Department of Clinical Veterinary Medicine, University of Bern, Länggassstrasse 128, Bern, 3001, Switzerland. 6. Vetsuisse Faculty, Clinic for Ruminants, University of Bern, Bremgartenstrasse 109a, Bern, 3012, Switzerland.
Abstract
OBJECTIVE: A novel congenital disorder affecting a calf was observed, and its phenotype and genetic mutation identified. ANIMAL: A six-month-old female Brown Swiss calf. METHODS: Diagnostic investigation and whole genome sequencing of a case parent trio was performed. RESULTS: The calf had a dull kinky coat with mild hypotrichosis, and teeth with brown staining and enamel defects. Histological examination of skin biopsies was compatible with a follicular dysplasia. Radiography and computed tomography revealed thickening of the skull bones and large pulp cavities with a marked thinning of enamel affecting all teeth. A de novo germline mutation affecting the distal-less homeobox gene (DLX3) was identified. The 10 bp frameshift mutation in exon 3 of the bovine DLX3 gene is predicted to replace the second C-terminal transactivation domain of the wild-type protein by a recoded peptide of 99 amino acids without any sequence similarity. CONCLUSION AND CLINICAL IMPORTANCE: A causative mutation for a sporadic phenotype resembling human tricho-dento-osseous syndrome was identified after detection of a de novo germline mutation in the DLX3 gene.
OBJECTIVE: A novel congenital disorder affecting a calf was observed, and its phenotype and genetic mutation identified. ANIMAL: A six-month-old female Brown Swiss calf. METHODS: Diagnostic investigation and whole genome sequencing of a case parent trio was performed. RESULTS: The calf had a dull kinky coat with mild hypotrichosis, and teeth with brown staining and enamel defects. Histological examination of skin biopsies was compatible with a follicular dysplasia. Radiography and computed tomography revealed thickening of the skull bones and large pulp cavities with a marked thinning of enamel affecting all teeth. A de novo germline mutation affecting the distal-less homeobox gene (DLX3) was identified. The 10 bp frameshift mutation in exon 3 of the bovineDLX3 gene is predicted to replace the second C-terminal transactivation domain of the wild-type protein by a recoded peptide of 99 amino acids without any sequence similarity. CONCLUSION AND CLINICAL IMPORTANCE: A causative mutation for a sporadic phenotype resembling human tricho-dento-osseous syndrome was identified after detection of a de novo germline mutation in the DLX3 gene.