OMIA:002382-9615 : Afibrinogenaemia, FGA-related in Canis lupus familiaris
Categories: Haematopoietic system phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 134820 (gene) , 202400 (trait)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2021
Species-specific description: Mischke et al. (2021): “we present a family of miniature wire-haired Dachshunds segregating for congenital afibrinogenemia. We employed homozygosity mapping, a genome-wide association study (GWAS), and sequencing of fibrinogen genes in order to identify a mutation responsible for afibrinogenemia.”
Mapping: Mischke et al. (2021): “ Homozygosity mapping and a genome-wide association study identified a candidate genomic region at 50,188,932–64,187,680 bp on CFA15 harboring FGB (fibrinogen beta chain), FGA (fibrinogen alpha chain), and FGG (fibrinogen gamma-B chain).”
Molecular basis: Mischke et al. (2021): “Sanger sequencing of all three fibrinogen genes in two cases and validation of the FGA-associated mutation (FGA:g.6296delT, NC_006597.3:g.52240694delA, rs1152388481) in pedigree members showed a perfect co-segregation with afibrinogenemia-affected phenotypes, obligate carriers, and healthy animals. In addition, the rs1152388481 variant was validated in 393 Dachshunds and samples from 33 other dog breeds. The rs1152388481 variant is predicted to modify the protein sequence of both FGA transcripts (FGA201:p.Ile486Met and FGA-202:p.Ile555Met) leading to proteins truncated by 306 amino acids.”
Clinical features: Mischke et al. (2021): “Three seven-week-old miniature wire-haired Dachshunds were presented … with excessive bleedings after fitting with a chip two days before. Two puppies were female and one male. One female died a few days later due to severe bleedings. The second female puppy survived up to an age of one year. Owners reported recurrent episodes with severe bleedings in the skin and gums. The third affected male puppy is under intensive veterinary care and still alive at the age of seven years despite intermittent severe bleeding episodes. … Case 4 … died from a hemoabdomen after a traumatic splenic rupture."
Pathology: Mischke et al. (2021): "In the affected dogs, PT [Prothrombin time](standard test), aPTT [activated partial thromboplastin time], and TT [thrombin time assay] exceeded the upper limits of detection (>200 s). PT measured with the optimized assay revealed increased or normal activities of factors II, V, VII, and X, respectively (case 1: 149%; case 2: 104%; case 3: 126%; 100% = average of normal adult dogs) and a moderate reduction in case 4 (44%, reference range in adult dogs: 75–130%). Fibrinogen concentration according to the coagulometric Clauss method was below the lowest detection limit in all four cases (<0.2 g/L; reference 1.0–3.0 g/L). Platelet count was normal in all four affected animals suffering from bleeding complications.”
Breed: Miniature Wirehaired Dachshund.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|FGA||fibrinogen alpha chain||Canis lupus familiaris||15||NC_051819.1 (52933990..52924743)||FGA||Homologene, Ensembl , NCBI gene|
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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.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1336||Miniature Wirehaired Dachshund||Afibrinogenaemia||FGA||deletion, small (<=20)||Naturally occurring variant||CanFam3.1||15||g.52240694del||c.1665delT||p.(I555Mfs*33)||Transcript XM_532697.6 / ENSCAFT00000043702.3||rs1152388481||rs1152388481||2021||34356081|
|2021||Mischke, R., Metzger, J., Distl, O. :|
|An FGA frameshift variant associated with afibrinogenemia in Dachshunds. Genes (Basel) 12:1065, 2021. Pubmed reference: 34356081 . DOI: 10.3390/genes12071065.|
- Created by Imke Tammen2 on 13 Aug 2021
- Changed by Imke Tammen2 on 13 Aug 2021