A deletion in GDF7 is associated with a heritable forebrain commissural malformation concurrent with ventriculomegaly and interhemispheric cysts in cats

Yoshihiko Yu, Erica K. Creighton, Reuben M. Buckley, Leslie A. Lyons, Reuben M. Buckley, Danielle Aberdein, Paulo C. Alves, Gregory S. Barsh, Rebecca R. Bellone, Tomas F. Bergström, Adam R. Boyko, Jeffrey A. Brockman, Margret L. Casal, Marta G. Castelhano, Ottmar Distl, Nicholas H. Dodman, N. Matthew Ellinwood, Jonathan E. Fogle, Oliver P. Forman, Dorian J. GarrickEdward I. Ginns, Jens Häggström, Robert J. Harvey, Daisuke Hasegawa, Bianca Haase, Christopher R. Helps, Isabel Hernandez, Marjo K. Hytönen, Maria Kaukonen, Christopher B. Kaelin, Tomoki Kosho, Emilie Leclerc, Teri L. Lear, Tosso Leeb, Ronald H.L. Li, Hannes Lohi, Maria Longeri, Mark A. Magnuson, Richard Malik, Shrinivasrao P. Mane, John S. Munday, William J. Murphy, Niels C. Pedersen, Simon M. Peterson-Jones, Max F. Rothschild, Clare Rusbridge, Beth Shapiro, Joshua A. Stern, William F. Swanson, Karen A. Terio, Rory J. Todhunter, Wesley C. Warren, Elizabeth A. Wilcox, Julia H. Wildschutte, Yoshihiko Yu, Leslie A. Lyons

Research output: Contribution to journalArticlepeer-review


An inherited neurologic syndrome in a family of mixed-breed Oriental cats has been characterized as forebrain commissural malformation, concurrent with ventriculomegaly and interhemispheric cysts. However, the genetic basis for this autosomal recessive syndrome in cats is unknown. 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. 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. This variant was not identified in 192 unaffected cats in the 99 Lives dataset. The variant segregated concordantly in an extended pedigree. In mice, GDF7 mRNA is expressed within the roof plate when commissural axons initiate ventrally-directed growth. This finding emphasized the importance of GDF7 in the neurodevelopmental process in the mammalian brain. A genetic test can be developed for use by cat breeders to eradicate this variant.

Original languageEnglish (US)
Article number672
Pages (from-to)1-15
Number of pages15
Issue number6
StatePublished - Jun 2020


  • BMP12
  • Brain malformation
  • Feline
  • Felis catus
  • Genetics
  • Genome-wide association study
  • Genomics
  • Mendelian traits
  • Neurodevelopment
  • Whole genome sequencing

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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