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Fetal anomalies

Gene: PKD1

Green List (high evidence)

PKD1 (polycystin 1, transient receptor potential channel interacting)
EnsemblGeneIds (GRCh38): ENSG00000008710
EnsemblGeneIds (GRCh37): ENSG00000008710
OMIM: 601313, Gene2Phenotype
PKD1 is in 15 panels

3 reviews

Eleanor Williams (Genomics England Curator)

Comment on mode of inheritance: updating MOI as biallelic cases have a more severe form of the disease
Created: 27 Jun 2019, 10:14 a.m. | Last Modified: 27 Jun 2019, 10:14 a.m.
Panel Version: 0.287

Julia Baptista (Royal Devon and Exeter NHS Foundation Trust)

Green List (high evidence)

Severe prenatal presentation can be caused both by monallelic or biallelic PKD1 variants.
Created: 3 Jun 2019, 2:06 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Publications

Rebecca Foulger (Genomics England curator)

Green List (high evidence)

Comment on mode of inheritance: Although not yet listed in DD-Gene2Phenotype, PKD1 is listed in OMIM with AD inheritance for Polycystic kidney disease 1, 173900. Monoallelic MOI was also listed in the original PAGE Additional gene list. However the external review and the two cited papers support both AD and AR inheritance for polycystic kidney disease (PKD). PMID:23624871 note that recessive polycystic kidney disease (ARPKD) frequently presents antenatally or in the neonatal period with severe renal involvement.
Created: 4 Jun 2019, 3:48 p.m.
PMID:23624871 (Gilbert et al., 2013) was added as a publication by Julia Baptista. The authors describe a male fetus with renal enlargement and oligohydramnios diagnosed at 27 weeks of gestation. This presentation resembled autosomal recessive PKD (ARPKD). Genetic analysis revealed a heterozygous truncating variant (p.Ser2788fs) in PKD1 inherited from the mother, and three unreported PKD1 variants inherited from the father. Although the authors don't exclude the possibility of a pathogenic variant in an additional gene, the paternally-inherited alleles support biallelic PKD1 alleles causing the fetal kidney anomalies.
Created: 4 Jun 2019, 3:47 p.m.
PMID:20558538 (Vujic et al., 2010) was added as a publication by Julia Baptista. The authors describe two pedigrees each with two patients with onset of polycystic kidney disease in-utero. Mutation analysis suggested that both families inherited, in trans, two incompletely penetrant PKD1 alleles, thus supporting autosomal recessive PKD.
Created: 4 Jun 2019, 3:46 p.m.
Comment on mode of inheritance: Updated the MOI from monoallelic to monoallelic AND biallelic, to match the review of Julia Baptista and evidence provided in PMID:20558538 (Vujic et al., 2010) and PMID:23624871 (Gilbert et al., 2013).
Created: 4 Jun 2019, 3:45 p.m.
This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as a Green gene.
Created: 24 Mar 2019, 4:30 p.m.
Disease confidence rating in PAGE Additional gene list: Confirmed. Mode of inheritance in PAGE list: monoallelic. Mode of pathogenicity in PAGE list: loss of function.
Created: 11 Dec 2018, 9:05 a.m.

History Filter Activity

12 Aug 2019, Gel status: 3

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene: PKD1 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

27 Jun 2019, Gel status: 3

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: PKD1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

4 Jun 2019, Gel status: 4

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene: PKD1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

4 Jun 2019, Gel status: 4

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene: PKD1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

4 Jun 2019, Gel status: 4

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: PKD1 were changed from Polycystic kidney disease 173900 to Polycystic kidney disease, 173900; Autosomal recessive polycystic kidney disease (ARPKD); Autosomal dominant polycystic kidney disease (ADPKD)

4 Jun 2019, Gel status: 4

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: PKD1 were set to

8 Nov 2018, Gel status: 4

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Rebecca Foulger (Genomics England curator)

gene: PKD1 was added gene: PKD1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE Additional Gene List Mode of inheritance for gene: PKD1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: PKD1 were set to Polycystic kidney disease 173900