OMIA 002208-9615 : Eye malformation, congenital in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 212550

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant with incomplete penetrance

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2019

Inheritance: Hug et al. (2019): "All cases traced back to the same male ancestor, but had quite diverse maternal lineages . . . . Seven out of 28 recorded puppies were affected and males and females were affected in equal proportions. As we could not identify any common ancestors in the maternal lines of the cases, we hypothesized an autosomal dominant inheritance with incomplete penetrance as the most likely mode of inheritance."

Molecular basis: By comparing the genome sequence of one affected Golden Retriever with the sequence of 601 control genomes, Hug et al. (2019) identified a "heterozygous private nonsense variant, c.487C>T . . . in the SIX6 gene. This variant is predicted to truncate about a third of the open reading frame, p.(Gln163*) . . . We hypothesize that the residual amount of functional SIX6 protein likely to be expressed in heterozygous dogs is sufficient to explain the observed incomplete penetrance and the varying severity of the eye defects in the affected dogs."

Prevalence: Hug et al. (2019): "All three available cases were heterozygous. Five additional close relatives including the common sire were also heterozygous, but did not show any obvious eye phenotypes. The variant was absent from the 464 unrelated Golden Retrievers and 17 non-affected siblings of the cases."

Breed: Golden Retriever.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
SIX6 SIX homeobox 6 Canis lupus familiaris 8 NC_006590.3 (35565838..35568423) SIX6 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
Golden Retriever Eye malformation, congenital SIX6 nonsense (stop-gain) CanFam3.1 8 g.35,566,504C>T c.487C>T p.(Gln163*) XM_547840.6:c.487C>T; XP_547840.3:p.(Gln163*) 2019 31207931

Reference


2019 Hug, P., Anderegg, L., Dürig, N., Lepori, V., Jagannathan, V., Spiess, B., Richter, M., Leeb, T. :
A <i>SIX6</i> Nonsense Variant in Golden Retrievers with Congenital Eye Malformations. Genes (Basel) 10:, 2019. Pubmed reference: 31207931. DOI: 10.3390/genes10060454.

Edit History


  • Created by Frank Nicholas on 12 Sep 2019
  • Changed by Frank Nicholas on 12 Sep 2019