A de novo variant in OTX2 in a lamb with otocephaly

Paris, Julia Maria; Letko, Anna; Häfliger, Irene Monika; Švara, Tanja; Gombač, Mitja; Klinc, Primož; Škibin, Andrej; Pogorevc, Estera; Drögemüller, Cord (2020). A de novo variant in OTX2 in a lamb with otocephaly. Acta Veterinaria Scandinavica, 62(1) BioMed Central Ltd. 10.1186/s13028-020-0503-z

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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 OTX2 genes.

Case presentation: A stillborn male lamb of the Istrian Pramenka sheep breed showed several congenital craniofacial 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 heterozygous single nucleotide variant in the OTX2 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 OTX2 open reading frame (p.Arg89*).

Conclusions: The genetic findings were consistent with the diagnosis of the otocephaly and provide strong evidence that the identified loss-of-function variant is pathogenic due to OTX2 haploinsufficiency. The benefits of trio-based whole-genome sequencing as an emerging tool in veterinary pathology to confirm diagnosis are highlighted.

Item Type:

Journal Article (Further Contribution)


05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

UniBE Contributor:

Paris, Julia Maria; Letko, Anna; Häfliger, Irene Monika and Drögemüller, Cord


600 Technology > 630 Agriculture
500 Science > 590 Animals (Zoology)
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health




BioMed Central Ltd.




Cord Drögemüller

Date Deposited:

04 Feb 2020 12:37

Last Modified:

10 Mar 2021 07:36

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