OMIA 001703-9913 : Chondrodysplasia, FGFR3-related in Bos taurus

In other species: sheep

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 100800 , 146000 , 187600 , 187601

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Dominant

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2020

Inheritance: Häfliger et al. (2020): "Considering that approximately 25% of offspring were affected, we assume that the sire is a germline mosaic for the variant but unfortunately no semen was available to confirm."

Molecular basis: Whole-genome sequencing of an affected calf and both its parents, followed by filtering of variants, enabled Häfliger et al. (2020) to identify a stop-lost mutation in FGFR3 as the likely causal variant, namely g.116,767,863C>A; NM_174318.3: c.2408G>T; [XM_024992994.1: p.(Ter803Leuext*93), which is "predicted to extend the sequence at the C‐terminal end with 93 additional amino acids". This variant resulted from a de novo mutation in the germline of the sire.

Clinical features: This disorder was first described by Drögemüller et al. (2006). As summarised by Häfliger et al. (2020): "a mild shortening of the upper jaw (brachygnathia superior) and an abnormal stature with movement disabilities owing to severe skeletal shortening of the limbs and hyperextension of the joints . . . . Furthermore, an examination of the profound shortened long bones of CD‐affected calves revealed a rarefication of primary spongiosa. Interestingly, there was no indication for irregularly arranged chondrocytes of epiphyseal plates . . . , as reported in other forms of bovine dwarfism or chondrodysplasia."

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
FGFR3 fibroblast growth factor receptor 3 Bos taurus 6 NC_037333.1 (116781176..116766308) FGFR3 Homologene, Ensembl, NCBI gene

Variants

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
Holstein Chondrodysplasia, disproportionate FGFR3 extension (stop-lost) ARS-UCD1.2 6 g.116,767,863C>A c.2408G>T p.(Ter803Leuext*93) NM_174318.3: c.2408G>T; [XM_024992994.1: p.(Ter803Leuext*93) 2020 32239744

References


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 Häfliger, I.M., Letko, A., Murgiano, L., Drögemüller, C. :
De novo stop-lost germline mutation in FGFR3 causes severe chondrodysplasia in the progeny of a Holstein bull. Anim Genet :, 2020. Pubmed reference: 32239744. DOI: 10.1111/age.12934.
2006 Drögemüller, C., Starke, A., Schmidbauer, S., Wohlsein, P. :
Kongenitaler disproportionaler Zwergwuchs bei Deutschen Holsteins Tierärztliche Praxis Ausgabe Grosstiere Nutztiere 34:148-154, 2006.

Edit History


  • Created by Frank Nicholas on 04 Apr 2020
  • Changed by Frank Nicholas on 04 Apr 2020
  • Changed by Frank Nicholas on 18 Apr 2020