OMIA 000628-9913 : Marfan syndrome in Bos taurus

Possibly relevant human trait(s) and/or gene(s) (MIM number): 154700

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Dominant

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2005

Species-specific name: Marfan Syndrome

Species-specific symbol: MFS

Species-specific description: Besser et al. (1990) reported a congenital syndrome of long, thin limbs, severe joint and tendon laxity, microspherophakia, ectopia lentis, heart murmurs and aortic dilatation in 7 calves, where all sired by a single phenotypically normal bull suspected of germline mosaicism for a new mutation resulting in this disease. One of the calves died with ruptured aorta at age 16 months. Histopathologic and electron microscopic studies of the aortic media of these calves demonstrated disorganized elastin and narrowed elastic lamina separated by widened spaces.

Parsons et al. (1992) with biochemical analyses on two calves with bovine Marfan syndrome showed that in contrast to elastin, collagen in aortae of Marfan calves was significantly higher than the mean of several controls These authors concluded that the microscopic and biochemical lesions of aortic elastin in bovine Marfan syndrome is likely due to defective microfibrillar metabolism. Absence of cystic medial necrosis in bovine Marfan aortae may explain normal elastin content in the animal model.

Potter et al. 1993 reported that Bovine Marfan syndrome is closely related to its human’s counterpart in its clinical signs and pathological lesions, suggesting similar metabolic defects for its cause. Major manifestations include ectopia lentis and aortic dilatation, aneurysm, and rupture. Similar to humans, affected cows have a defect in fibrillin metabolism (Potter et al. 1994). Potter et al. 1993 suggested that the bovine Marfan syndrome, like the human disorder, is caused by a mutation in fibrillin, leading to defective microfibrillar synthesis (Mohammad Shariflou 6/11/2006).

Mapping: The cDNA sequence of the bovine FBN1 gene was characterized and somatic-cell-hybrid mapped to syntenic group U5, which corresponds to chromosome BTA10, by Tilstra et al. (1994) (Mohammad Shariflou 6/11/2006). Thue and Buchanen (2003) confirmed this result by linkage mapping a SNP in the FBN1 gene to chromosome BTA10, "10 cM from BM888 (LOD = 4.88) and 14 cM from INRA096 (LOD = 3.77)."

Molecular basis: By sequencing the cDNA of the almost certain comparative candidate gene (based on the homologous human disorder), namely FBN1, in affected Limousin calves, Singleton et al. (2005) discovered the causal mutation in this breed to be a 3598G>A transition in exon 29, resulting in a likely substitution of a glutamic acid by lysine at position 1200 as the cause of this syndrome (Mohammad Shariflou 6/11/2006).

Hirano et al. (2012) reported a "G>A mutation at the intron64 splicing accepter site (c.8227-1G>A)" as being causative for Marfan disease in Japanese Black cattle. "The mutation causes a 1-base shift of the intron64 splicing accepter site to the 3′ direction, and a 1-base deletion in processed mRNA. This 1-base deletion creates a premature termination codon, and a 125-amino acid shorter Fibrillin-1 protein is produced from the mutant mRNA."

Breeds: Japanese Black, Limousin.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
FBN1 fibrillin 1 Bos taurus 10 NC_037337.1 (61654541..61919167) FBN1 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
Limousin Marfan syndrome FBN1 missense UMD3.1 10 g.62054844G>A c.3598G>A p.E1200K 2005 15776436 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool
Japanese Black Marfan syndrome FBN1 splicing UMD3.1 10 g.62141462 c.8227-1G>A 2012 22221020 Variant information kindly provided or confirmed by Hubert Pausch, including information from Additional Table 6 of Jansen et al. (2013) BMC Genomics201314:446 https://doi.org/10.1186/1471-2164-14-446

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.
2019 Zepeda-Batista, J.L., Parra-Bracamonte, G.M., Núñez-Domínguez, R., Ramírez-Valverde, R., Ruíz-Flores, A., Zepeda-Batista, J.L., Parra-Bracamonte, G.M., Núñez-Domínguez, R., Ramírez-Valverde, R., Ruíz-Flores, A. :
Screening genetic diseases prevalence in Braunvieh cattle. Trop Anim Health Prod 51:25-31, 2019. Pubmed reference: 30014197. DOI: 10.1007/s11250-018-1655-y.
2012 Hirano, T., Matsuhashi, T., Kobayashi, N., Watanabe, T., Sugimoto, Y. :
Identification of an FBN1 mutation in bovine Marfan syndrome-like disease. Anim Genet 43:11-7, 2012. Pubmed reference: 22221020. DOI: 10.1111/j.1365-2052.2011.02209.x.
2005 Singleton, AC., Mitchell, AL., Byers, PH., Potter, KA., Pace, JM. :
Bovine model of Marfan syndrome results from an amino acid change (c.3598G > A, p.E1200K) in a calcium-binding epidermal growth factor-like domain of fibrillin-1. Hum Mutat 25:348-52, 2005. Pubmed reference: 15776436. DOI: 10.1002/humu.20152.
2003 Thue, TD., Buchanan, FC. :
Linkage mapping of FBN1 to bovine chromosome 10. Anim Genet 34:150, 2003. Pubmed reference: 12648102.
1999 Gigante, A., Chillemi, C., Potter, K.A., Bertoni-Freddari, C., Greco, F. :
Elastic fibers of musculoskeletal tissues in bovine Marfan syndrome: A morphometric study Journal of Orthopaedic Research 17:624-628, 1999. Pubmed reference: 10459772. DOI: 10.1002/jor.1100170424.
1998 Masabanda, J., Ewald, D., Buitkamp, J., Potter, K., Fries, R. :
Molecular markers for the bovine fibrillin 1 gene (FBN1) map to 10q26. Anim Genet 29:460-1, 1998. Pubmed reference: 9883511.
1997 Rosenbloom, J., Abrams, WR., Kucich, U., Decker, S., Mecham, R., Macarak, E., Howard, P. :
Expression of microfibrillar proteins by bovine bladder urothelium. Urology 49:287-92, 1997. Pubmed reference: 9037301. DOI: 10.1016/S0090-4295(96)00437-2.
1996 Pessier, A.P., Potter, K.A. :
Ocular pathology in bovine marfans syndrome with demonstration of altered fibrillin immunoreactivity in explanted ciliary body cells Laboratory Investigation 75:87-95, 1996. Pubmed reference: 8683943.
1994 Potter, K.A., Besser, T.E. :
Cardiovascular lesions in bovine Marfan syndrome Veterinary Pathology 31:501-509, 1994. Pubmed reference: 7801427.
Tilstra, D.J., Li, L., Potter, K.A., Womack, J., Byers, P.H. :
Sequence of the coding region of the bovine fibrillin cDNA and localization to bovine chromosome 10 Genomics 23:480-485, 1994. Pubmed reference: 7835900. DOI: 10.1006/geno.1994.1527.
1993 Potter, K.A., Hoffman, Y., Sakai, L.Y., Byers, P.H., Besser, T.E., Milewicz, D.M. :
Abnormal fibrillin metabolism in bovine Marfan syndrome. Am J Pathol 142:803-10, 1993. Pubmed reference: 8456941.
1992 Parsons, J.C., Hoffman, Y., Potter, K.A., Besser, T.E. :
Normal Elastin Content of Aorta in Bovine Marfan Syndrome Experimental and Molecular Pathology 57:145-152, 1992. Pubmed reference: 1426158.
1990 Besser, T.E., Potter, K.A., Bryan, G.M., Knowlen, G.G. :
An Animal Model of the Marfan Syndrome American Journal of Medical Genetics 37:159-165, 1990. Pubmed reference: 2240037. DOI: 10.1002/ajmg.1320370137.

Edit History


  • Created by Mohammad Shariflou on 06 Nov 2006
  • Changed by Frank Nicholas on 06 Dec 2011
  • Changed by Frank Nicholas on 09 Dec 2011
  • Changed by Frank Nicholas on 26 Nov 2012
  • Changed by Frank Nicholas on 07 Jun 2013
  • Changed by Frank Nicholas on 15 Aug 2016