PKD1 Nonsense Variant in a Lagotto Romagnolo Family with Polycystic Kidney Disease

被引:2
作者
Drogemuller, Michaela [1 ]
Klein, Nadine [2 ]
Steffensen, Rikke Lill [3 ]
Keiner, Miriam [4 ]
Jagannathan, Vidhya [1 ]
Leeb, Tosso [1 ]
机构
[1] Univ Bern, Inst Genet, Vetsuisse Fac, CH-3001 Bern, Switzerland
[2] Tierarztl Praxis Kleintiere, Dickstrasse 57, D-53773 Hennef, Sieg, Germany
[3] Schlitterweg 6, D-61191 Rosbach, Germany
[4] Justus Liebig Univ, Small Anim Clin, Internal Med, D-35392 Giessen, Germany
关键词
Canis lupus familiaris; dog; whole genome sequencing; de novo; precision medicine; HRFCD; ADPKD; animal model; EXPRESSION; MUTATION; GENETICS; GENOMICS; ADPKD; LIVER;
D O I
10.3390/genes14061210
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
A female Lagotto Romagnolo dog with polycystic kidney disease (PKD) and her progeny, including PKD-affected offspring, were studied. All affected dogs appeared clinically inconspicuous, while sonography revealed the presence of renal cysts. The PKD-affected index female was used for breeding and produced two litters with six affected offspring of both sexes and seven unaffected offspring. The pedigrees suggested an autosomal dominant mode of inheritance of the trait. A trio whole genome sequencing analysis of the index female and her unaffected parents identified a de novo heterozygous nonsense variant in the coding region of the PKD1 gene. This variant, NM_001006650.1:c.7195G>T, is predicted to truncate 44% of the open reading frame of the wild-type PKD1 protein, NP_001006651.1:p.(Glu2399*). The finding of a de novo variant in an excellent functional candidate gene strongly suggests that the PKD1 nonsense variant caused the observed phenotype in the affected dogs. Perfect co-segregation of the mutant allele with the PKD phenotype in two litters supports the hypothesized causality. To the best of our knowledge, this is the second description of a PKD1-related canine form of autosomal dominant PKD that may serve as an animal model for similar hepatorenal fibrocystic disorders in humans.
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共 27 条
  • [1] Expression of PKD1 and PKD2 transcripts and proteins in human embryo and during normal kidney development
    Chauvet, V
    Qian, F
    Boute, N
    Cai, YQ
    Phakdeekitacharoen, B
    Onuchic, LF
    Attié-Bitach, T
    Guicharnaud, L
    Devuyst, O
    Germino, GG
    Gubler, MC
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2002, 160 (03) : 973 - 983
  • [2] A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3
    Cingolani, Pablo
    Platts, Adrian
    Wang, Le Lily
    Coon, Melissa
    Tung Nguyen
    Wang, Luan
    Land, Susan J.
    Lu, Xiangyi
    Ruden, Douglas M.
    [J]. FLY, 2012, 6 (02) : 80 - 92
  • [3] Type of PKD1 Mutation Influences Renal Outcome in ADPKD
    Cornec-Le Gall, Emilie
    Audrezet, Marie-Pierre
    Chen, Jian-Min
    Hourmant, Maryvonne
    Morin, Marie-Pascale
    Perrichot, Regine
    Charasse, Christophe
    Whebe, Bassem
    Renaudineau, Eric
    Jousset, Philippe
    Guillodo, Marie-Paule
    Grall-Jezequel, Anne
    Saliou, Philippe
    Ferec, Claude
    Le Meur, Yannick
    [J]. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2013, 24 (06): : 1006 - 1013
  • [4] A splice site variant in INPP5E causes diffuse cystic renal dysplasia and hepatic fibrosis in dogs
    Dillard, Kati J.
    Hytonen, Marjo K.
    Fischer, Daniel
    Tanhuanpaa, Kimmo
    Lehti, Mari S.
    Vainio-Siukola, Katri
    Sironen, Anu
    Anttila, Marjukka
    [J]. PLOS ONE, 2018, 13 (09):
  • [5] Renal plasticity revealed through reversal of polycystic kidney disease in mice
    Dong, Ke
    Zhang, Chao
    Tian, Xin
    Coman, Daniel
    Hyder, Fahmeed
    Ma, Ming
    Somlo, Stefan
    [J]. NATURE GENETICS, 2021, 53 (12) : 1649 - +
  • [6] Distribution and developmentally regulated expression of murine polycystin
    Geng, L
    Segal, Y
    Pavlova, A
    Barros, EJG
    Lohning, C
    Lu, WN
    Nigam, SK
    Frischauf, AM
    Reeders, ST
    Zhou, J
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 1997, 272 (04) : F451 - F459
  • [7] A Non-Synonymous Mutation in the Canine Pkd1 Gene Is Associated with Autosomal Dominant Polycystic Kidney Disease in Bull Terriers
    Gharahkhani, Puya
    O'Leary, Caroline A.
    Kyaw-Tanner, Myat
    Sturm, Richard A.
    Duffy, David L.
    [J]. PLOS ONE, 2011, 6 (07):
  • [8] Cilia and centrosomes: A unifying pathogenic concept for cystic kidney disease?
    Hildebrandt, F
    Otto, E
    [J]. NATURE REVIEWS GENETICS, 2005, 6 (12) : 928 - 940
  • [9] THE POLYCYSTIC KIDNEY-DISEASE-1 (PKD1) GENE ENCODES A NOVEL PROTEIN WITH MULTIPLE CELL RECOGNITION DOMAINS
    HUGHES, J
    WARD, CJ
    PERAL, B
    ASPINWALL, R
    CLARK, K
    SANMILLAN, JL
    GAMBLE, V
    HARRIS, PC
    [J]. NATURE GENETICS, 1995, 10 (02) : 151 - 160
  • [10] A comprehensive biomedical variant catalogue based on whole genome sequences of 582 dogs and eight wolves
    Jagannathan, V
    Droegemueller, C.
    Leeb, T.
    Aguirre, Gustavo
    Andre, Catherine
    Bannasch, Danika
    Becker, Doreen
    Davis, Brian
    Drogemuller, Cord
    Ekenstedt, Kari
    Faller, Kiterie
    Forman, Oliver
    Friedenberg, Steve
    Furrow, Eva
    Giger, Urs
    Hitte, Christophe
    Hytonen, Marjo
    Lohi, Hannes
    Mellersh, Cathryn
    Mickelson, James R.
    Murgiano, Leonardo
    Oberbauer, Anita
    Schmutz, Sheila
    Schoenebeck, Jeffrey
    Summers, Kim
    van Steenbeek, Frank
    Wade, Claire
    [J]. ANIMAL GENETICS, 2019, 50 (06) : 695 - 704