ClinGen Dosage Sensitivity Curation Page

PKD1

  • Curation Status: Complete

Location Information

Select assembly: (NC_000016.9) (NC_000016.10)
Evidence for haploinsufficiency phenotype
PubMed ID Description
25491204 In 2014, Choi et al. used LR-PCR on 20 unrelated Korean patients diagnosed with autosomal dominant polycystic kidney disease (ADPKD) to identify loss of function variants in PKD1 and PKD2. The results of LR-PCR demonstrated that 10 probands possessed pathogenic loss of function variants in PKD1 as well as a family history of ADPKD; 6 of these probands had frameshift variants, while the other 3 probands had nonsense variants.
24694054 In 2014, Obeidova et al. used methods including LR-PCR, nested PCR, and direct sequencing on 56 unrelated Czech patients diagnosed with autosomal dominant polycystic kidney disease (ADPKD) to identify loss of function variants in PKD1 and PKD2. Their study demonstrated that 37 probands possessed likely pathogenic variants in PKD1. These variants included 11 frameshift variants, 9 nonsense variants, 3 splice variants, and 4 small deletions and insertions in frame. For a group of probands with loss of function variants in PKD1, PKD1 was demonstrated to be the cause of ADPKD in their families through linkage analyses.
29529603 In 2018, Xu et al. used LR-PCR and next generation sequencing (NGS) on 120 Chinese families with at least one family member being diagnosed with autosomal dominant polycystic kidney disease (ADPKD) to describe novel variants in PKD1 and PKD2. The results of LR-PCR and NGS revealed 51 novel variants and 34 known variants in PKD1. These variants included 24 nonsense variants, 32 frameshift variants, 3 in-frame deletions, 2 large deletions, and 5 splices.

Haploinsufficiency phenotype comments:

Heterozygous loss of function mutations in the PKD1 gene cause autosomal dominant polycystic kidney disease (ADPKD) [GeneReviews]. There are several studies reporting the mutation frequency and spectrum in a number of ethnic populations (PMIDs 22237240, 22185115, 19686598, 11571556, 11558899). Partial- or whole-gene deletions have been described in a small number of cases (~4%, GeneReviews). Large heterozygous deletions, involving the PKD1 and the adjacent TSC2 gene, result in the TSC2/PKD1 contiguous gene syndrome (PKDTS) [PMIDs 22169896, 18818683, 14695542, 17185137). PKDTS has been identified in patients with tuberous sclerosis complex (TSC) and early-onset severe autosomal dominant polycystic kidney disease (ADPKD).

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

No literature identified.