Congenital Malformations in a Holstein-Fresian Calf with a Unique Mosaic Karyotype: A Case Report

SIMPLE SUMMARY: Congenital malformations, defined as defects of morphogenesis present at birth, are an important problem in livestock production, if they are caused by hereditary mutations. They can lead to animal death, reduce their productive ability and influence animal welfare. Thus, the identification of the causes of congenital abnormalities are greatly needed. In the present report, we described a Holstein-Fresian calf with multiple congenital malformations including head asymmetry, the relocation of the frontal sinus and eye orbits, hypoplastic thymus, ductus Botalli, unfinished obliteration in umbilical arteries, and a bilateral series of tooth germs in the temporal region. Cytogenetic examination revealed a unique mosaic karyotype with a small marker chromosome, which could not be identified by standard banding techniques. It can be assumed that the presence the marker chromosome may be associated with observed congenital malformations in the studied calf. ABSTRACT: A Holstein-Fresian calf with multiple congenital malformations was subjected postmortem to anatomical and genetic investigation. The calf was small (20 kg), had shortened limbs and was unable to stand up. It lived only 44 days. Detailed anatomical investigation revealed the following features: head asymmetry, the relocation of the frontal sinus and eye orbits, hypoplastic thymus without neck part, ductus Botalli, unfinished obliteration in umbilical arteries, and a bilateral series of tooth germs in the temporal region. Cytogenetic examination, performed on in vitro cultured fibroblasts, showed a unique mosaic karyotype with a marker chromosome—60,XX[9 2%]/60,XX,+mar[8%], which was for the first time described in cattle. No other chromosome abnormalities indicating chromosome instabilities, like chromatid breaks or gaps were identified, thus teratogenic agent exposure during pregnancy was excluded. The marker chromosome (mar) was small and it was not possible to identify its origin, however, sequential DAPI/C (4’,6-diamidino-2-phenylindole) band staining revealed a large block of constitutive heterochromatin, which is characteristic for centromeric regions of bovine autosomes. We suppose that the identified marker chromosome was a result of somatic deletion in an autosome and its presence could be responsible for the observed developmental malformations. In spite of the topographic distance among the affected organs, we expected a relationship between anatomical abnormalities. To the of our best knowledge, this is the first case of a mosaic karyotype with a cell line carrying a small marker chromosome described in a malformed calf.