OMIA 002176-9940 : Meckel-like hepatorenal fibrocystic dysplasia syndrome in Ovis aries

Possibly relevant human trait(s) and/or gene(s) (MIM number): 607361

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2018

Molecular basis: Stayner et al. (2017) reported two almost adjacent missense mutations (p.Ile681Asn and p.Ile687Ser) in complete linkage disequilibrium (and which can, therefore, be regarded as a single variant) within the TMEM67 gene as being likely causal of this disorder in two flocks (one Perendale and one Coopworth) located 500 kms apart and with no history of interbreeding within the last 40 years.

Clinical features: Stayner et al. (2017): "The kidney and liver abnormalities in the affected lambs were similar to those observed in the Meckel/Joubert/Nephronophthisis constellation of abnormalities in humans."

Pathology: Stayner et al. (2017): "Meckelin protein was expressed in affected and unaffected kidney epithelial cells by immunoblotting, and in primary cilia of lamb kidney cyst epithelial cells by immunofluorescence. In contrast to primary cilia of relatively consistent length and morphology in unaffected kidney cells, those of affected cyst-lining cells displayed a range of short and extremely long cilia, as well as abnormal morphologies, such as bulbous regions along the axoneme. Putative cilia fragments were also consistently located within the cyst luminal contents. The abnormal ciliary phenotype was further confirmed in cultured interstitial fibroblasts from affected kidneys. These primary cilia dysmorphologies and length control defects were significantly greater in affected cells compared to unaffected controls."

Breeds: Coopworth, Perendale.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
TMEM67 transmembrane protein 67 Ovis aries 9 NC_040260.1 (91677988..91633536) TMEM67 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
Coopworth Perendale Meckel-like hepatorenal fibrocystic dysplasia syndrome TMEM67 haplotype OARv3.1 9 c.(2050T>A; 2068T>G p.(Ile681Asn; Ile687Ser) 2017 28487520

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.
2017 Stayner, C., Poole, C.A., McGlashan, S.R., Pilanthananond, M., Brauning, R., Markie, D., Lett, B., Slobbe, L., Chae, A., Johnstone, A.C., Jensen, C.G., McEwan, J.C., Dittmer, K., Parker, K., Wiles, A., Blackburne, W., Leichter, A., Leask, M., Pinnapureddy, A., Jennings, M., Horsfield, J.A., Walker, R.J., Eccles, M.R. :
An ovine hepatorenal fibrocystic model of a Meckel-like syndrome associated with dysmorphic primary cilia and TMEM67 mutations. Sci Rep 7:1601, 2017. Pubmed reference: 28487520. DOI: 10.1038/s41598-017-01519-4.
2005 Johnstone, AC., Davidson, BI., Roe, AR., Eccles, MR., Jolly, RD. :
Congenital polycystic kidney disease in lambs. N Z Vet J 53:307-14, 2005. Pubmed reference: 16220122. DOI: 10.1080/00480169.2005.36565.

Edit History


  • Created by Frank Nicholas on 15 Mar 2019
  • Changed by Frank Nicholas on 15 Mar 2019