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

Preview

Text Paris et al OTX2 ActaVetScand2020.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (1MB) | Preview

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.

Interest & Impact

Downloads

120 since deposited on 04 Feb 2020
16 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item