COL4A5 mutation causes Alport syndrome with focal segmental glomerulosclerosis lesion: Case report and literature review

Zhang, Ping; Zhuo, Ling; Zou, Yurong; Li, Guisen; Peng, Kun

doi:10.5414/cn109737

Cited by 7 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mutations in COL4A3 and COL4A4 are known to cause Alport syndrome (AS), a thin basement membrane nephropathy resulting in pathognomonic glomerular basement membrane, and secondary FSGS is known to develop in classic AS at later stages of the disease (45). For COL4A5, which may be affected by mutations causing AS with FSGS lesions (46), its expression was found to be shared between different cell subpopulations: podocytes, vascular smooth muscle cells, and mesangial cells. At the podocyte level, the application highlighted the specific expression of CRB2 (alias Crumbs Cell Polarity Complex Component 2), a family component of the Crumbs cell polarity complex known to be affected by mutations in FSGS (47).…”

Section: Online Results Visualization and The Development Of An Interamentioning

confidence: 99%

Text Mining Gene Selection to Understand Pathological Phenotype Using Biological Big Data

2021

View full text Add to dashboard Cite

Whole transcriptome omics experiments allow for the study of gene regulation at the cellular level. During analysis and interpretation of omics data, false discovery can occur. To minimize false discovery and identify true significant cases, multi-test correction has been introduced to bioinformatics algorithms. The scientific literature offers a huge collection of information that can be parsed using a web Application Programming Interface. Gene selection by text mining can rank information according to its importance while taking into account the most recent updates in scientific literature. The integration of text mining selection in biological big data, such as transcriptome experiments including single cell transcriptome, can achieve an important dimensional reduction of the data without any statistical hypothesis. This avoids false discoveries regarding the molecules of interest. Hydatidiform moles and focal segmental glomerulosclerosis (FSGS) nephropathy are the two examples presented in this chapter, which demonstrate the considerable value of these analytical methods to prove the concept. The best FSGS markers expressed can be displayed by building an interactive online web interface as a web resource based on the glomerular cell transcriptome.

show abstract

Section: Online Results Visualization and The Development Of An Interamentioning

confidence: 99%

Text Mining Gene Selection to Understand Pathological Phenotype Using Biological Big Data

2021

View full text Add to dashboard Cite

show abstract

“…Male patients with truncating mutations develop ESKD at approximately 20 years old, while those with non-truncating mutations develop ESKD at 40. It is worth noting that XLAS, caused by COL4A5 mutations, has considerable phenotypic heterogeneity and a combination of phenotypes (21)(22)(23)(24). It may not even show typical clinical phenotypes (such as hematuria, proteinuria, and hearing and vision problems) or AS-like pathological changes, which is not conducive to early diagnosis and effective intervention (11).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, in young patients with unexplained glomerular diseases, without typical manifestations, clinicians also need to consider COL4A5 mutations. Genetic testing, based on next-generation sequencing, is crucial for the diagnosis of XLAS, which is a disease with high phenotypic and genetic heterogeneity (21)(22)(23)25).…”

Section: Discussionmentioning

confidence: 99%

Case report: Preimplantation genetic testing for X-linked alport syndrome caused by variation in the COL4A5 gene

Liu,

Wen,

et al. 2023

Front. Pediatr.

View full text Add to dashboard Cite

X-Linked Alport Syndrome (XLAS) is an X-linked, dominant, hereditary nephropathy mainly caused by mutations in the COL4A5 gene, found on chromosome Xq22. In this study, we reported a pedigree with XLAS caused by a COL4A5 mutation. This family gave birth to a boy with XLAS who developed hematuria and proteinuria at the age of 1 year. We used next-generation sequencing (NGS) to identify mutations in the proband and his parents and confirmed the results using Sanger sequencing. This testing showed there was a single nucleotide missense variation, c.3659G>A (p.Gly1220Asp) (NM_033380.3), in the COL4A5 gene. To prevent the inheritance of the syndrome, we used eight embryos for trophoblast biopsy after assisted reproductive technology treatment, and whole genome amplification (WGA) was performed using multiple annealing and looping-based amplification cycles (MALBAC). Embryos were subjected to Preimplantation Genetic Testing (PGT) procedures, including Sanger sequencing, NGS-based single nucleotide polymorphism (SNP) haplotype linkage analysis, and chromosomal copy number variation (CNV) analysis. The results showed that three embryos (E1, E2, and E4) were free of CNV and genetic variation in the COL4A5 gene. Embryo E1 (4AA) was transferred after consideration of the embryo growth rate, morphology, and PGT results. Prenatal diagnosis in the second trimester showed that the fetus had a normal karyotype and did not carry the COL4A5 mutation (c.3659G>A). Ultimately, a healthy boy was born and did not carry the pathogenic COL4A5 mutation, which indicated that PGT prevented the intergenerational transmission of the causative mutation of XLAS.

show abstract

“…Key components of its scaffolding are Collagen IV α3α4α5 trimers (Naylor et al, 2021). Alport syndrome is caused by mutations in the genes that encode these Collagen type IV alpha proteins ( COL4A3 , COL4A4 , and COL4A5 ) (Artuso et al, 2012; Barker et al, 1990; Cameron-Christie et al, 2019; Fallerini et al, 2014; Hadjipanagi et al, 2022; Heiskari et al, 1996; Hudson, 2004; Longo et al, 2006; Pokidysheva et al, 2021; Zhang et al, 2019). The mutations inhibit trimeric protein complex formation which prevents a pivotal developmental switch from Collagen type IV α1 and α2 isoforms in fetal kidney to the α3, α4, and α5 isoforms in mature podocytes (Harvey et al, 1998; Kalluri et al, 1997; Miner and Sanes, 1994).…”

Section: Introductionmentioning

confidence: 99%

ADrosophilamodel to screen Alport syndromeCOL4A5variants for their functional pathogenicity

Duan,

Wen,

Zhao

et al. 2024

Preprint

View full text Add to dashboard Cite

Alport syndrome is a hereditary chronic kidney disease, attributed to rare pathogenic variants in either of three collagen genes (COL4A3/4/5) with most localized inCOL4A5. Trimeric type IV Collagen α3α4α5 is essential for the glomerular basement membrane that forms the kidney filtration barrier. A means to functionally assess the many candidate variants and determine pathogenicity is urgently needed. We usedDrosophila, an established model for kidney disease, and identifyCol4a1as the functional homolog of humanCOL4A5in the fly nephrocyte (equivalent of human podocyte). Fly nephrocytes deficient forCol4a1showed an irregular and thickened basement membrane and significantly reduced nephrocyte filtration function. This phenotype was restored by expressing human reference (wildtype)COL4A5, but not byCOL4A5carrying any of three established pathogenic patient-derived variants. We then screened seven additional patientCOL4A5variants; their ClinVar classification was either likely pathogenic or of uncertain significance. The findings support pathogenicity for four of these variants; the three others were found benign. Thus, demonstrating the effectiveness of thisDrosophilain vivo kidney platform in providing the urgently needed variant-level functional validation.

show abstract

COL4A5 mutation causes Alport syndrome with focal segmental glomerulosclerosis lesion: Case report and literature review

Cited by 7 publications

References 0 publications

Text Mining Gene Selection to Understand Pathological Phenotype Using Biological Big Data

Text Mining Gene Selection to Understand Pathological Phenotype Using Biological Big Data

Case report: Preimplantation genetic testing for X-linked alport syndrome caused by variation in the COL4A5 gene

ADrosophilamodel to screen Alport syndromeCOL4A5variants for their functional pathogenicity

Contact Info

Product

Resources

About