OMIA 002227-9940 : Otocephaly, OTX2-related in Ovis aries

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 610125 , 613986

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Dominant

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2020

Molecular basis: Highlighting the power of whole-genome sequencing of trios (a single affected individual and its parents), Paris et al. (2020) identified "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*)."

Clinical features: Paris et al. (2020): "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."

Breed: Istrian Pramenka.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
OTX2 orthodenticle homeobox 2 Ovis aries 7 NC_040258.1 (71486762..71477074) OTX2 Homologene, Ensembl, NCBI gene

Variants

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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Istrian Pramenka Otocephaly OTX2 nonsense (stop-gain) Oar_rambouillet_v1.0 7 g.71478714G>A c.265C>T p.(Arg89*) Paris et al. (2020): XM_015097088.2:c.265C > T 2020 31969185

Reference


2020 Paris, J.M., Letko, A., Häfliger, I.M., Švara, T., Gombač, M., Klinc, P., Škibin, A., Pogorevc, E., Drögemüller, C. :
A de novo variant in OTX2 in a lamb with otocephaly. Acta Vet Scand 62:5, 2020. Pubmed reference: 31969185. DOI: 10.1186/s13028-020-0503-z.

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  • Created by Frank Nicholas on 25 Jan 2020