OMIA 002173-9615 : Diffuse cystic renal dysplasia and hepatic fibrosis in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 213300

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2018

Cross-species summary: This disorder is classified as a Hepatorenal fibrocystic disorder (HRFCD)

Inheritance: Dillard et al. (2018): "The pedigree of the affected puppies was suggestive of an autosomal recessive inheritance"

Molecular basis: Dillard et al. (2018) identified "a case-specific homozygous splice donor site variant in a cilia related gene, INPP5E: c.1572+5G>A. . . . We observed that the identified variant introduces a novel splice site in INPP5E causing a frameshift and formation of a premature stop codon."

Clinical features: Dillard et al. (2018) reported "a novel lethal ciliopathy in Norwich Terrier puppies that was diagnosed at necropsy and characterized as diffuse cystic renal disease and hepatic fibrosis"

Pathology: Dillard et al. (2018): "The histopathological findings were typical for cystic renal dysplasia in which the cysts were located in the straight portion of the proximal tubule, and thin descending and ascending limbs of Henle’s loop."

Prevalence: Dillard et al. (2018) "genotyped the [INPP5E:c.1572+5G>A] variant in a cohort of 480 Finnish Norwich Terriers. No other homozygous dogs were found in this cohort while 29 of the analyzed dogs were heterozygous and the association of the variant to the disease was significant (p = 8,377 x 10^−37). The carrier frequency was 6% (29/483) and all carrier dogs were close relatives to the affected puppies . . . . In addition, the variant was investigated in 200 dogs from 69 breeds and 3 wolves using publicly available whole genome sequencing data . . . . The variant was not observed in any of the samples."

Breed: Norwich Terrier.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
INPP5E inositol polyphosphate-5-phosphatase E Canis lupus familiaris 9 NC_006591.3 (49061014..49071474) INPP5E Homologene, Ensembl, NCBI gene

Variants

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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.

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
Norwich Terrier Diffuse cystic renal dysplasia and hepatic fibrosis INPP5E splicing CanFam3.1 9 g.49069064G>A c.1572+5G>A Dillard et al. (2018): "the identified variant introduces a novel splice site in INPP5E causing a frameshift and formation of a premature stop codon." 2018 30235266

Reference


2018 Dillard, K.J., Hytönen, M.K., Fischer, D., Tanhuanpää, K., Lehti, M.S., Vainio-Siukola, K., Sironen, A., Anttila, M. :
A splice site variant in INPP5E causes diffuse cystic renal dysplasia and hepatic fibrosis in dogs. PLoS One 13:e0204073, 2018. Pubmed reference: 30235266. DOI: 10.1371/journal.pone.0204073.

Edit History


  • Created by Frank Nicholas on 02 Mar 2019
  • Changed by Frank Nicholas on 02 Mar 2019