Julia Maria Paris (Author), Anna Letko (Author), Irene Monika Häflinger (Author), Tanja Švara (Author), Mitja Gombač (Author), Primož Klinc (Author), Andrej Škibin (Author), Estera Pogorevc (Author), Cord Drögemüller (Author)

Abstract

Background:Otocephaly is a rare lethal malformation of the first branchial arch. While the knowledge on the causes of otocephaly in animals is limited, different syndromic forms in man are associated with variants of the PRRX1 and OT X2 genes.Case presentation:A stillborn male lamb of the Istrian Pramenka sheep breed showed several congenital crani-ofacial anomalies including microstomia, agnathia, aglossia, and synotia. In addition, the lamb had a cleft palate, a small opening in the ventral neck region, a cystic oesophagus and two hepatic cysts. The brain was normally developed despite the deformed shape of the head. Taken together the findings led to a diagnosis of otocephaly. Whole-genome sequencing was performed from DNA of the affected lamb and both parents revealing a heterozy-gous single nucleotide variant in the OT X2 gene (Chr7: 71478714G > A). The variant was absent in both parents and therefore due to a de novo mutation event. It was a nonsense variant, XM_015097088.2:c.265C > T; which leads to an early premature stop codon and is predicted to truncate more than 70% of the OT X2 open reading frame (p.Arg89*).Conclusions:The genetic findings were consistent with the diagnosis of the otocephaly and provide strong evi-dence that the identified loss-of-function variant is pathogenic due to OT X2 haploinsufficiency. The benefits of trio-based whole-genome sequencing as an emerging tool in veterinary pathology to confirm diagnosis are highlighted.

Keywords

Whole Genome Sequencing;

Data

Language: English
Year of publishing:
Typology: 1.03 - Short Scientific Article
Organization: UL VF - Veterinary Faculty
UDC: 636.09:616
COBISS: 4930682 Link will open in a new window
ISSN: 1751-0147
Views: 613
Downloads: 374
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Other data

Secondary keywords: Animals, Domestic;Microstomia;Precision Medicine;Rare Diseases;
Type (COBISS): Article
Pages: str. 1-6
Volume: ǂVol. ǂ62
Issue: ǂart. ǂ5
Chronology: 2020
DOI: 10.1186/s13028-020-0503-z
ID: 11784360