Genetic Testing in Pediatric Kidney Disease

Arora, Veronica; Anand, Kanav; Verma, Ishwar C.

doi:10.1007/s12098-020-03198-y

Cited by 17 publications

(14 citation statements)

References 25 publications

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“…32,33 The emergence of NGS has resulted in a very large number of papers on single-gene contributions to kidney disease. 34 Several hundred genes have now been identified that may contribute to the development and progression of CKD. 35 All of the NGS approaches listed have contributed to our understanding of specific genes and disease pathways involved in CKD.…”

Section: Next Generation Sequencing (Ngs) To Identify Genes In Ckd: R...mentioning

confidence: 99%

Emerging Role of Clinical Genetics in CKD

et al. 2022

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Section: Next Generation Sequencing (Ngs) To Identify Genes In Ckd: R...mentioning

confidence: 99%

Emerging Role of Clinical Genetics in CKD

et al. 2022

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“…Congenital anomalies of the kidney and urinary tract (CAKUT) comprise a clinically wide spectrum of malformations and are among most identified prenatal defect, accounting for up to 23% of overall birth defects 1,2 . CAKUT can present as an isolated renal condition or as a part of a syndrome 3 . The incidence of CAKUT is approximately 1 to 4 per 1000 pregnancies 3 .…”

Section: Ključne Riječi Prirođene Anomalije;mentioning

confidence: 99%

Congenital anomalies of the kidney and urinary tract (CAKUT)

2022

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“…While genetic testing is crucial for confirmation of the AS diagnosis, its use poses several challenges [ 7 , 8 ]. One is the phenotypic spectrum exhibited by individuals heterozygous for COL4A4 or COL4A3 variants.…”

Section: Introductionmentioning

confidence: 99%

COL4A4 variant recently identified: lessons learned in variant interpretation—a case report

et al. 2022

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Background Alport syndrome is a hereditary kidney disease characterized by hematuria and proteinuria. Although there have been reports of autosomal dominant COL4A4 variants, this is likely an underdiagnosed condition. Improved access to affordable genetic testing has increased the diagnosis of Alport syndrome. As genetic testing becomes ubiquitous, it is imperative that clinical nephrologists understand the benefits and challenges associated with clinical genetic testing. Case Presentation We present a family of Mexican descent with a heterozygous COL4A4 variant (c.5007delC, ClinVar accession numbers: SCV001580980.2, SCV001993731.1) not previously discussed in detail in the literature. The proband received a biopsy diagnosis suggestive of Fabry disease 18 years after she first developed hematuria and progressed to chronic kidney disease stage III. One year later, the proband was provisionally diagnosed with Alport syndrome after a variant of uncertain significance in the COL4A4 gene was identified following targeted family variant testing of her daughter. Upon review of the medical histories of the proband’s children and niece, all but one had the same variant. Of the four with the variant, three display clinical symptoms of hematuria, and/or proteinuria. The youngest of the four, only months old, has yet to exhibit clinical symptoms. Despite these findings there was a considerable delay in synthesizing this data, as patients were tested in different commercial genetic testing laboratories. Subsequently, understanding this family’s inheritance pattern, family history, and clinical symptoms, as well as the location of the COL4A4 variant resulted in the upgrade of the variant’s classification. Although the classification of this variant varied among different clinical genetic testing laboratories, the consensus was that this variant is likely pathogenic. Conclusions This COL4A4 variant (c.5007delC) not yet discussed in detail in the literature is associated with Alport syndrome. The inheritance pattern is suggestive of autosomal dominant inheritance. This report highlights the intricacies of variant interpretation and classification, the siloed nature of commercial genetic testing laboratories, and the importance of a thorough family history for proper variant interpretation. Additionally, the cases demonstrate the varied clinical presentations of Alport syndrome and suggest the utility of early screening, diagnosis, monitoring, and treatment.

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Genetic Testing in Pediatric Kidney Disease

Cited by 17 publications

References 25 publications

Emerging Role of Clinical Genetics in CKD

Emerging Role of Clinical Genetics in CKD

Congenital anomalies of the kidney and urinary tract (CAKUT)

COL4A4 variant recently identified: lessons learned in variant interpretation—a case report

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