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Precise variant interpretation, phenotype ascertainment, and genotype-phenotype correlation of children in the EARLY PRO-TECT Alport trial

Early initiation of therapy in patients with Alport syndrome (AS) slows down renal failure by many years. Genotype-phenotype correlations propose that the location and character of the individual's variant correlate with the renal outcome and any extra renal manifestations. In-depth clinical an...

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Main Authors: Böckhaus, Jan Simon (Author) , Höfele, Julia (Author) , Riedhammer, Korbinian M. (Author) , Tönshoff, Burkhard (Author) , Ehren, Rasmus (Author) , Pape, Lars (Author) , Latta, Kay (Author) , Fehrenbach, Henry (Author) , Lange-Sperandio, Bärbel (Author) , Kettwig, Matthias (Author) , Hoyer, Peter (Author) , Staude, Hagen (Author) , Konrad, Martin (Author) , John-Kroegel, Ulrike (Author) , Gellermann, Jutta (Author) , Hoppe, Bernd (Author) , Galiano, Matthias (Author) , Gessner, Michaela (Author) , Pohl, Michael (Author) , Bergmann, Carsten (Author) , Friede, Tim (Author) , Gross, Oliver (Author)
Format: Article (Journal)
Language:English
Published: 2021
In: Clinical genetics
Year: 2021, Volume: 99, Issue: 1, Pages: 143-156
ISSN:1399-0004
DOI:10.1111/cge.13861
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1111/cge.13861
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/cge.13861
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Author Notes:Jan Boeckhaus, Julia Hoefele, Korbinian M. Riedhammer, Burkhard Tönshoff, Rasmus Ehren, Lars Pape, Kay Latta, Henry Fehrenbach, Baerbel Lange-Sperandio, Matthias Kettwig, Peter Hoyer, Hagen Staude, Martin Konrad, Ulrike John, Jutta Gellermann, Bernd Hoppe, Matthias Galiano, Michaela Gessner, Michael Pohl, Carsten Bergmann, Tim Friede, Oliver Gross for the GPN Study Group and EARLY PRO-TECT Alport Investigators
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Summary:Early initiation of therapy in patients with Alport syndrome (AS) slows down renal failure by many years. Genotype-phenotype correlations propose that the location and character of the individual's variant correlate with the renal outcome and any extra renal manifestations. In-depth clinical and genetic data of 60/62 children who participated in the EARLY PRO-TECT Alport trial were analyzed. Genetic variants were interpreted according to current guidelines and criteria. Genetically solved patients with X-linked inheritance were then classified according to the severity of their COL4A5 variant into less-severe, intermediate, and severe groups and disease progress was compared. Almost 90% of patients were found to carry (likely) pathogenic variants and classified as genetically solved cases. Patients in the less-severe group demonstrated a borderline significant difference in disease progress compared to those in the severe group (p = 0.05). While having only limited power according to its sample size, an obvious strength is the precise clinical and genetic data of this well ascertained cohort. As in published data differences in clinical progress were shown between patients with COL4A5 less-severe and severe variants. Therefore, clinical and segregational data are important for variant (re)classification. Genetic testing should be mandatory allowing early diagnosis and therapy of AS.
Item Description:"First published: 11 October 2020".- Frontdoor des Artikels
Gesehen am 15.08.2024
Physical Description:Online Resource
ISSN:1399-0004
DOI:10.1111/cge.13861

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