Related Experiment Video
Updated: Jun 14, 2025
Array Comparative Genomic Hybridization Array CGH for Detection of Genomic Copy Number Variants
Published on: February 21, 2015
Alport Syndrome: Clinical Utility of Early Genetic Diagnosis in Children
Vasileia Christodoulaki1,2, Konstantina Kosma1, Nikolaos M Marinakis1,3
1Laboratory of Medical Genetics, Medical School, National and Kapodistrian University of Athens (NKUA), 11527 Athens, Greece.
Insights
Genetic diagnosis of Alport syndrome (AS) using Whole Exome Sequencing enables early intervention with Renin-Angiotensin-Aldosterone System (RAAS) inhibitors. This approach helps delay chronic kidney disease progression, particularly in pediatric patients.
Area of Science:
- Nephrology
- Genetics
- Pediatrics
Background:
- Alport syndrome (AS) is a hereditary kidney disease caused by mutations in COL4A3, COL4A4, and COL4A5 genes.
- Progression to end-stage renal disease (ESRD) can be delayed by Renin-Angiotensin-Aldosterone System (RAAS) inhibitors.
Purpose of the Study:
- To evaluate the utility of Whole Exome Sequencing (WES) for diagnosing Alport syndrome.
- To assess the impact of genetic diagnosis on early therapeutic intervention and patient management, especially in children.
Main Methods:
- Whole Exome Sequencing (WES) was performed on 19 patients with AS phenotype.
- Genetic testing was extended to at-risk family members through cascade screening.
- Patients were classified based on genetic diagnosis: X-linked AS (XLAS), autosomal dominant AS (ADAS), and autosomal recessive AS (ARAS).
Main Results:
- Genetic diagnoses included 5 XLAS males, 5 XLAS females, 6 ADAS, and 1 ARAS.
- Cascade screening identified additional carriers: 4 XLAS males, 8 XLAS females, 6 ADAS, and 3 ARAS heterozygotes.
- Fifteen patients were eligible for RAAS inhibitor treatment post-diagnosis; others were advised for follow-up.
Conclusions:
- Genetic diagnosis of AS is crucial for timely initiation of treatment and monitoring.
- Early intervention, particularly with RAAS inhibitors, can delay chronic kidney disease progression.
- Genetic testing and subsequent management are especially vital for the pediatric population affected by Alport syndrome.
Abstract:
Alport syndrome (AS) is a hereditary glomerulopathy due to pathogenic variants in COL4A3, COL4A4, and COL4A5. Treatment with Renin-Angiotensin-Aldosterone System (RAAS) inhibitors can delay progression to end stage renal disease (ESRD). From 2018 until today, we performed Whole Exome Sequencing (WES) in 19 patients with AS phenotype with or without positive family history. Fourteen of these patients were children. Genetic testing was extended to family members at risk. All patients received a genetic diagnosis of AS: five X-linked AS (XLAS) males, five X-linked AS (XLAS) females, six autosomal dominant AS (ADAS), and one autosomal recessive AS (ARAS). After cascade screening four XLAS males and eight XLAS females, six ADAS and three ARAS heterozygotes were added to our initial results. Fifteen patients were eligible to start treatment with RAAS inhibitors after their diagnosis. All XLAS female patients, ARAS heterozygotes, and ADAS have been advised to be followed up, so that therapeutic intervention can begin in the presence of microalbuminuria. Genetic diagnosis of AS ensures early therapeutic intervention and appropriate follow up to delay progression to chronic kidney disease, especially in thet pediatric population.
