Monoallelic pathogenic IFT140 variants are a common cause of autosomal dominant polycystic kidney disease-spectrum phenotype
© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA..
Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder, characterized by development and enlargement of kidney cysts, eventually leading to end-stage kidney disease (ESKD). Pathogenic variants in the PKD1 and PKD2 genes are the major cause of ADPKD; additional rare variants in the GANAB, DNAJB11, ALG5 and ALG9 genes have been found in a minority of ADPKD patients. More recently, a significant number of ADPKD families have been linked to monoallelic variants in the IFT140 gene.
Methods: In this retrospective study, we tested the prevalence of the known causative genes of ADPKD-spectrum phenotype, including the PKD1, PKD2, GANAB, DNAJB11, ALG5, ALG and IFT140 genes, in a cohort of 129 ADPKD patients who consecutively underwent genetic testing in a single centre in Italy. Genetic testing utilized a combination of targeted next-generation sequencing, long-range polymerase chain reaction, Sanger sequencing and multiplex ligation-dependent probe amplification. Clinical evaluation was conducted through renal function testing and imaging features, including ultrasonography, computer tomography and magnetic resonance imaging.
Results: Of the 129 enrolled patients, 86 (66.7%) had pathogenic variants in PKD1 and 28 (21.7%) in PKD2, loss of function pathogenic variants in the IFT140 gene were found in 3 unrelated patients (2.3%), no pathogenic variants were found in other ADPKD genes and 12 patients (9.3%) remained genetically unresolved (ADPKD-GUR). Familial clinical and genetic screening of the index patients with ADPKD due to an IFT140 pathogenic variant (ADPKD-IFT140) allowed identification of eight additional affected relatives. In the 11 ADPKD-IFT140 patients, the renal phenotype was characterized by mild and late-onset PKD, with large renal cysts and limited kidney insufficiency. Extrarenal manifestations, including liver cysts, were rarely seen.
Conclusion: Our data suggest the monoallelic pathogenic IFT140 variants are the third most common cause of the ADPKD-spectrum phenotype in Italy, usually associated with a mild and atypical renal cystic disease.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
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| Enthalten in: |
Clinical kidney journal - 17(2024), 2 vom: 22. Feb., Seite sfae026 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dordoni, Chiara [VerfasserIn] |
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| Links: |
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| Themen: |
ADPKD |
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| Anmerkungen: |
Date Revised 27.02.2024 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1093/ckj/sfae026 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368943364 |
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| 245 | 1 | 0 | |a Monoallelic pathogenic IFT140 variants are a common cause of autosomal dominant polycystic kidney disease-spectrum phenotype |
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| 520 | |a © The Author(s) 2024. Published by Oxford University Press on behalf of the ERA. | ||
| 520 | |a Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder, characterized by development and enlargement of kidney cysts, eventually leading to end-stage kidney disease (ESKD). Pathogenic variants in the PKD1 and PKD2 genes are the major cause of ADPKD; additional rare variants in the GANAB, DNAJB11, ALG5 and ALG9 genes have been found in a minority of ADPKD patients. More recently, a significant number of ADPKD families have been linked to monoallelic variants in the IFT140 gene | ||
| 520 | |a Methods: In this retrospective study, we tested the prevalence of the known causative genes of ADPKD-spectrum phenotype, including the PKD1, PKD2, GANAB, DNAJB11, ALG5, ALG and IFT140 genes, in a cohort of 129 ADPKD patients who consecutively underwent genetic testing in a single centre in Italy. Genetic testing utilized a combination of targeted next-generation sequencing, long-range polymerase chain reaction, Sanger sequencing and multiplex ligation-dependent probe amplification. Clinical evaluation was conducted through renal function testing and imaging features, including ultrasonography, computer tomography and magnetic resonance imaging | ||
| 520 | |a Results: Of the 129 enrolled patients, 86 (66.7%) had pathogenic variants in PKD1 and 28 (21.7%) in PKD2, loss of function pathogenic variants in the IFT140 gene were found in 3 unrelated patients (2.3%), no pathogenic variants were found in other ADPKD genes and 12 patients (9.3%) remained genetically unresolved (ADPKD-GUR). Familial clinical and genetic screening of the index patients with ADPKD due to an IFT140 pathogenic variant (ADPKD-IFT140) allowed identification of eight additional affected relatives. In the 11 ADPKD-IFT140 patients, the renal phenotype was characterized by mild and late-onset PKD, with large renal cysts and limited kidney insufficiency. Extrarenal manifestations, including liver cysts, were rarely seen | ||
| 520 | |a Conclusion: Our data suggest the monoallelic pathogenic IFT140 variants are the third most common cause of the ADPKD-spectrum phenotype in Italy, usually associated with a mild and atypical renal cystic disease | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ADPKD | |
| 650 | 4 | |a IFT140 | |
| 650 | 4 | |a genetic kidney disease | |
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| 650 | 4 | |a polycystic kidney disease | |
| 700 | 1 | |a Zeni, Letizia |e verfasserin |4 aut | |
| 700 | 1 | |a Toso, Diego |e verfasserin |4 aut | |
| 700 | 1 | |a Mazza, Cinzia |e verfasserin |4 aut | |
| 700 | 1 | |a Mescia, Federica |e verfasserin |4 aut | |
| 700 | 1 | |a Cortinovis, Roberta |e verfasserin |4 aut | |
| 700 | 1 | |a Econimo, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Savoldi, Gianfranco |e verfasserin |4 aut | |
| 700 | 1 | |a Alberici, Federico |e verfasserin |4 aut | |
| 700 | 1 | |a Scolari, Francesco |e verfasserin |4 aut | |
| 700 | 1 | |a Izzi, Claudia |e verfasserin |4 aut | |
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