Kidney enlargement and multiple liver cyst formation implicate mutations in <i>PKD1/2</i> in adult sporadic polycystic kidney disease

Fujimaru, Takuya; Mori, Takayasu; Sekine, Akinari; Mandai, Shintaro; Chiga, Motoko; Kikuchi, Hiroaki; Ando, Fumiaki; Mori, Yutaro; Nomura, Naohiro; Iimori, Soichiro; Naito, Seiji; Okado, Tomokazu; Rai, Tatemitsu; Hoshino, Junichi; Ubara, Yoshifumi; Uchida, Shinichi; Sohara, Eisei

doi:10.1111/cge.13249

Cited by 22 publications

(21 citation statements)

References 49 publications

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“…We performed a percutaneous renal biopsy; histologically, six of 16 glomeruli displayed global sclerosis, along with mild cellular infiltration, conspicuous interstitial fibrosis, renal tubular atrophy, and cystoid irregular dilation (Figure ), suggesting an NPHP diagnosis. We performed targeted sequencing using a next‐generation sequencer, with the approval by the research ethics committee of Tokyo Medical and Dental University in accordance with the Declaration of Helsinki and the patient's written informed consent. A homozygous full gene deletion of NPHP1 (NM_000272.3:g110879716‐110962709) was resultantly identified, as well as heterozygous substitutions in PKD1 (NM_0001009944.2:c.6395T>G(p.Phe2132Cys)) (Figure ), BBS1 (NM_024649.4:c.908T>C(p.Val303Ala)) , and INPP5E (NM_019892.4:c.1652C>T(p.Thr551Met)) .…”

Section: Case Reportmentioning

confidence: 99%

Section: Case Reportmentioning

confidence: 99%

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PKD1 mutation may epistatically ameliorate nephronophthisis progression in patients with NPHP1 deletion

Watanabe

Ino

Fujimaru

et al. 2019

Clinical Case Reports

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Key Clinical Message We report a patient with adult‐onset nephronophthisis (NPHP) that was identified a homozygous full gene deletion of NPHP1 and a heterozygous PKD1 mutation. We suggest that the PKD1 mutation may have epistatically ameliorated NPHP disease progression and that the screening of larger cohorts for similar possible epistatic effects is needed.

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Section: Case Reportmentioning

confidence: 99%

Section: Case Reportmentioning

confidence: 99%

PKD1 mutation may epistatically ameliorate nephronophthisis progression in patients with NPHP1 deletion

Watanabe

Ino

Fujimaru

et al. 2019

Clinical Case Reports

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“…We previously identified PKD1 or PKD2 mutation in 60.4% of PKD patients without an apparent family history [5]. These findings suggested a difference of genetic characteristics between PKD patients with a family history and those with no family history.…”

Section: Introductionmentioning

confidence: 89%

“…Among them, 45 patients have been reported in our previous report [5]. Patients with childhood-onset PKD were not included.…”

Section: Patientsmentioning

confidence: 99%

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Genotype-Clinical Correlations in Polycystic Kidney Disease with No Apparent Family History

Sekine¹,

Fujimaru²,

Hoshino³

et al. 2019

Am J Nephrol

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Background: Genetic characteristics of polycystic kidney disease (PKD) patients without apparent family history were reported to be different from those with a positive family history. However, the clinical course of PKD patients with no apparent family history is not well documented in the literature. Methods: We evaluated the relationship between genotype and the clinical course of 62 PKD patients with no apparent family history. Results: The annual decline of renal function was faster in the patients with PKD1/PKD2 mutation (PKD1 truncating [–3.08; 95% CI –5.30 to –0.87, p = 0.007], PKD1 nontruncating [–2.10; –3.82 to –0.38, p = 0.02], and PKD2 [–2.31; –4.40 to –0.23, p = 0.03]) than in the other patients without PKD1/PKD2 mutation. Similar results were obtained after adjustment for gender, age, estimated glomerular filtration rate (eGFR), height-adjusted total kidney volume (TKV), and mean arterial pressure (MAP). There was no significant difference in the annual decline of renal function among the different PKD1/PKD2 groups, but Kaplan-Meier analysis showed that progression to eGFR < 15 mL/min/1.73 m² was significantly faster in PKD1 truncating group (p = 0.05). The annual rate of TKV increase was larger in the patients with PKD1/PKD2 mutation (PKD1 truncating [4.63; 95% CI 0.62–8.64, p = 0.03], PKD1 nontruncating [3.79; 0.55–7.03, p = 0.02], and PKD2 [2.11; –1.90 to 6.12, p = 0.29]) than in the other patients without PKD1/PKD2 mutation. Similar results were obtained after adjustment for gender, age, eGFR, and MAP. Conclusion: Detection of PKD1/PKD2 mutation, especially PKD1 truncating, is useful for predicting the renal outcome and rate of TKV increase in PKD patients with no apparent family history.

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OFD1: One gene, several disorders

Pezzella

Bove

Tammaro

et al. 2022

American J of Med Genetics Pt C

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The OFD1 protein is necessary for the formation of primary cilia and left–right asymmetry establishment but additional functions have also been ascribed to this multitask protein. When mutated, this protein results in a variety of phenotypes ranging from multiorgan involvement, such as OFD type I (OFDI) and Joubert syndromes (JBS10), and Primary ciliary dyskinesia (PCD), to the engagement of single tissues such as in the case of retinitis pigmentosa (RP23). The inheritance pattern of these condition differs from X‐linked dominant male‐lethal (OFDI) to X‐linked recessive (JBS10, PCD, and RP23). Distinctive biological peculiarities of the protein, which can contribute to explain the extreme clinical variability and the genetic mechanisms underlying the different disorders are discussed. The extensive spectrum of clinical manifestations observed in OFD1‐mutated patients represents a paradigmatic example of the complexity of genetic diseases. The elucidation of the mechanisms underlying this complexity will expand our comprehension of inherited disorders and will improve the clinical management of patients.

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Kidney enlargement and multiple liver cyst formation implicate mutations in PKD1/2 in adult sporadic polycystic kidney disease

Cited by 22 publications

References 49 publications

PKD1 mutation may epistatically ameliorate nephronophthisis progression in patients with NPHP1 deletion

PKD1 mutation may epistatically ameliorate nephronophthisis progression in patients with NPHP1 deletion

Genotype-Clinical Correlations in Polycystic Kidney Disease with No Apparent Family History

OFD1: One gene, several disorders

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