COL4A gene variants are common in children with hematuria and a family history of kidney disease

Rheault, Michelle N.; McLaughlin, Heather; Mitchell, Asia; Blake, Lauren E.; Devarajan, Prasad; Warady, Bradley A.; Gibson, Keisha; Lieberman, Kenneth V.

doi:10.1007/s00467-023-05993-z

Cited by 6 publications

(1 citation statement)

References 26 publications

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“…Table 1 reports diagnostic yields for targeted panels which are disease-specific, ranging from 6.8% for patients with renal stones [28] to 81% for patients with a clinical diagnosis of Autosomal Dominant Polycystic Kidney Disease (ADPKD) [26]. In the case of non-specific CKD clinical presentations, diagnostic yield from panels range from 28 to 40% for pediatric cases [37,38], 21 to 65% for pediatric/adult cases [39][40][41] and 12 to 56% for adult cases.…”

Section: Targeted Panel Technologymentioning

confidence: 99%

Genomic Approaches for Monogenic Kidney Diseases: A Comparative Review of Diagnostic Methods and Precision Medicine Implications

Giovanella,

Ligabue,

Chester

et al. 2023

Applied Sciences

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Chronic kidney disease is a long-term condition with significant implications for quality of life and health care costs. To uncover the etiology in selected cases suspected of monogenicity, a genomic approach can be employed. There are multiple technologies available, but there is currently no consensus on the most effective diagnostic approach. This review provides a comparison of currently available diagnostic methods in terms of diagnostic yield. However, the heterogeneity of patient cohort inclusion criteria limits direct comparisons. Our review identified three studies which compared a targeted gene panel and whole-exome sequencing for the same patient population. However, the results are inconclusive due to the different sizes and specificity of the targeted panels employed. The contribution of a whole-genome sequencing approach is highly debated. It is noteworthy that a large number of data are generated by these sequencing technologies. This allows for rapid analysis of coding and non-coding regions. However, the interpretation of variants is a significant burden, and the reporting of incidental findings is still challenging. Therefore, the identification of the most efficient technology is pivotal but still controversial. To conclude, an objective comparison of the three methods for the same population could overcome the limits of these studies’ heterogeneity and highlight the weaknesses and the strengths of individual approaches.

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Section: Targeted Panel Technologymentioning

confidence: 99%

Genomic Approaches for Monogenic Kidney Diseases: A Comparative Review of Diagnostic Methods and Precision Medicine Implications

Giovanella,

Ligabue,

Chester

et al. 2023

Applied Sciences

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Detection of Alport gene variants in children and young people with persistent haematuria

Ng,

Yamamura,

Shenoy

et al. 2024

Pediatr Nephrol

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Background Genetic kidney disease is an important cause of persistent microscopic haematuria in children and young people. We aimed to determine the frequency of variants in the Alport syndrome genes (COL4A3, COL4A4 or COL4A5) in individuals under 18 years of age presenting with persistent microscopic haematuria to a single specialist centre in the UK over a 10-year period. Methods We conducted a retrospective longitudinal study of individuals referred to a tertiary paediatric nephrology service with persistent microscopic haematuria between April 2012 to 2022. Results A total of 224 individuals (female 51.8%) were evaluated with persistent microscopic haematuria of greater than 6 months duration. The age at presentation was 7.5 ± 4.3 years (mean ± SD) with a duration of follow-up of 6.8 ± 4.6 years (mean ± SD). Targeted exome sequencing was performed in 134 individuals and 91 (68%) had a pathogenic or likely pathogenic variant in COL4A3, COL4A4 or COL4A5. Only 49.5% of individuals with identified variants had a family history of microscopic haematuria documented and 37.4% (34/91) had additional proteinuria at presentation. COL4A5 was the most common gene affected and missense variants affecting glycine residues were the most common variant type. Conclusion Over two-thirds of children and young people who underwent genetic testing had an identifiable genetic basis for their microscopic haematuria and over half did not have a documented family history. Genetic testing should be part of the evaluation of persistent microscopic haematuria despite a negative family history. Graphical abstract

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Whole exome sequencing approach for identification of the molecular etiology in pediatric patients with hematuria

Wu,

Cui,

Liu

et al. 2024

Clinica Chimica Acta

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COL4A gene variants are common in children with hematuria and a family history of kidney disease

Cited by 6 publications

References 26 publications

Genomic Approaches for Monogenic Kidney Diseases: A Comparative Review of Diagnostic Methods and Precision Medicine Implications

Genomic Approaches for Monogenic Kidney Diseases: A Comparative Review of Diagnostic Methods and Precision Medicine Implications

Detection of Alport gene variants in children and young people with persistent haematuria

Whole exome sequencing approach for identification of the molecular etiology in pediatric patients with hematuria

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