OMIA 000478-9685 : Holoprosencephaly in Felis catus

In other species: horse , pig , sheep

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 236100 , 157170 , 142945 , 142946 , 609637 , 605934 , 610828 , 609408 , 610829 , 614226

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2020

Cross-species summary: Developmental failure of cleavage of the forebrain (prosencephalon); with a deficit in midline facial development, and with cyclopia (see MIA 000249) in the severe form.

History: As summarised by Yu et al. (2020), "In an effort to develop a breed of cats [Toyger] having similar phenotypes to a tiger, including a small rounded ear, a mixed breed cat derived from the Oriental cat breed was discovered to have small rounded ears and hence, was used as a foundation sire for a breeding program. Outcross and backcross breeding indicated the phenotype was autosomal recessive [Keating et al., 2016]. However, a magnetic resonance imaging (MRI) examination of a kitten with the desired ear phenotype, which had an accidental head injury from a fall, indicated the presence of congenital hydrocephalus. Additional MRIs of the breeding stock suggested cats with the ear phenotype had congenital brain malformations. These cats have small rounded ear pinnae and doming of the head . . . . This extended family of mixed-breed cats derived from the Oriental breed has been characterized clinically and histopathologically with forebrain commissural malformation concurrent with ventriculomegaly and interhemispheric cysts. . . . As a result of the potentially harmful impacts associated with the trait, the breeder promptly discontinued the breeding program".

Inheritance: Keating et al. (2016) provided evidence consistent with autosomal recessive inheritance.

Mapping: Yu et al. (2020): "Forty-three cats were genotyped on the Illumina Infinium Feline 63K iSelect DNA Array and used for analyses. Genome-wide association studies, including a sib-transmission disequilibrium test and a case-control association analysis, and homozygosity mapping, identified a critical region on cat chromosome A3."

Molecular basis: Yu et al. (2020): "Short-read whole genome sequencing was completed for a cat trio segregating with the syndrome. A homozygous 7 bp deletion in growth differentiation factor 7 (GDF7) (c.221_227delGCCGCGC [p.Arg74Profs]) was identified in affected cats, by comparison to the 99 Lives Cat variant dataset, validated using Sanger sequencing and genotyped by fragment analyses. . . . The variant segregated concordantly in an extended pedigree."

Clinical features: "Ventriculomegaly with frequent concomitant supratentorial interhemispheric, communicating ventricular type-1b cysts and multiple midline and callosal malformations were detected in all cats displaying neurologic signs" (Keating et al., 2016)

Prevalence: Yu et al. (2020): "This variant was not identified in 192 unaffected cats in the 99 Lives dataset."

Breed: Toyger.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
GDF7 growth differentiation factor 7 Felis catus A3 NC_018725.2 (124737756..124732610) GDF7 Homologene, Ensembl, NCBI gene


By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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
Toyger Holoprosencephaly GDF7 deletion, small (<=20) Felis_catus_9.0 A3 g.127002233_127002239delGCCGCGC c.221_227delGCCGCGC p.(Arg74Profs*17) "a 7 bp deletion in the coding region of GDF7 (c.221_227delGCCGCGC [p.Arg74Profs*17]) at the position A3:127002233 (ENSFCAT00000063603)" (Yu et al., 2020) 2020 32575532


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2020 Lyons, L.A. :
Precision medicine in cats-The right biomedical model may not be the mouse! PLoS Genet 16:e1009177, 2020. Pubmed reference: 33290388. DOI: 10.1371/journal.pgen.1009177.
Yu, Y., Creighton, E.K., Buckley, R.M., Lyons, L.A. :
A Deletion in <i>GDF7</i> is Associated with a Heritable Forebrain Commissural Malformation Concurrent with Ventriculomegaly and Interhemispheric Cysts in Cats. Genes (Basel) 11:, 2020. Pubmed reference: 32575532. DOI: 10.3390/genes11060672.
2016 Keating, M.K., Sturges, B.K., Sisó, S., Wisner, E.R., Creighton, E.K., Lyons, L.A. :
Characterization of an Inherited Neurologic Syndrome in Toyger Cats with Forebrain Commissural Malformations, Ventriculomegaly and Interhemispheric Cysts. J Vet Intern Med 30:617-26, 2016. Pubmed reference: 26846816. DOI: 10.1111/jvim.13836.

Edit History

  • Created by Frank Nicholas on 13 Apr 2016
  • Changed by Frank Nicholas on 13 Apr 2016
  • Changed by Frank Nicholas on 26 Jun 2020