A de novo variant in OTX2 in a lamb with otocephaly

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

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.

• Jezik: Angleški jezik
• Ključne besede: Agnathia, microstomia, precision medicine, rare disease, synotia, whole-genome sequencing, sheep
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.03 - Kratki znanstveni prispevek
• Organizacija: VF - Veterinarska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2020
• Št. strani: Str. 1-6
• Številčenje: Vol. 62, no. e5
• PID: 20.500.12556/RUL-116670
• UDK: 636.09:616
• ISSN pri članku: 1751-0147
• DOI: 10.1186/s13028-020-0503-z
• COBISS.SI-ID: 4930682
• Datum objave v RUL: 02.06.2020

Gradivo je del revije

• Naslov: Acta veterinaria Scandinavica
• Skrajšan naslov: Acta vet. Scand.
• Založnik: BioMed Central
• ISSN: 1751-0147
• COBISS.SI-ID: 515671577

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 02.06.2020