Alport syndrome (AS) is the second-most frequent monogenic kidney disease and 85% of cases are caused by mutations in the genes of the α5 chains of collagen type IV (COL4A5). The early diagnosis and treatment are essential for the prognosis of AS. The clinical phenotypes of AS are very variable, which is challenging to diagnose. Genetic diagnosis is sensitive and accurate, which can recognize the affected individuals with mild phenotype for early diagnosis and predict the age at renal failure for early treatment. In addition, genetic testing will offer the available reproductive options, including prenatal diagnosis and preimplantation genetic testing (PGT). In this study, three novel COL4A5 variants (c.1834G > T, c.865G > A and c.1032 + 5G > A) were found. These variants co-segregated with the disease in multiple affected family members. In vitro splicing assay indicated that the c.1032 + 5G > A variant resulted in aberrant splicing involving exon 18 skipping. The healthy babies without these novel COL4A5 variants were born by PGT or prenatal diagnosis, respectively. Three novel variants in COL4A5 gene can provide insights into further genetic counseling or genotype-phenotype correlations.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890855 | PMC |
| http://dx.doi.org/10.1038/s41598-025-92649-7 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Identification of novel COL4A5 variants and prenatal diagnosis in three large families.
Sci Rep
March 2025
Department of Medical Genetics, Jiangxi Maternal and Child Health Hospital, Nanchang, China.
Alport syndrome (AS) is the second-most frequent monogenic kidney disease and 85% of cases are caused by mutations in the genes of the α5 chains of collagen type IV (COL4A5). The early diagnosis and treatment are essential for the prognosis of AS. The clinical phenotypes of AS are very variable, which is challenging to diagnose.
View Article and Find Full Text PDFMolecular Review of Suspected Alport Syndrome Patients-A Single-Centre Experience.
Genes (Basel)
February 2025
Department of Medical Genetics, The Children's Memorial Health Institute, 04-730 Warsaw, Poland.
Alport syndrome (AS) is a clinically and genetically heterogeneous glomerulopathy resulting from pathogenic variants in and . Genetic diagnosis is increasingly being conducted using next-generation sequencing (NGS). Within eight years, we examined a group of 247 Polish individuals and found in total 138 unrelated probands suspected with AS based on clinical course, laboratory findings, and/or family history, as well as the total of 109 family members.
View Article and Find Full Text PDFCorneal endothelial neovascularization and glaucoma in X-linked Alport syndrome.
Eur J Ophthalmol
February 2025
Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China.
Introduction: Variants in are responsible for X-linked Alport syndrome. It is characterized by kidney disease, sensorineural hearing loss and variable ocular abnormalities. In this case, a woman with corneal endothelial neovascularization, glaucoma, nuclear cataract, temporal retinal thinning, and renal defects was identified with a variant in .
View Article and Find Full Text PDFEffects of a Novel COL4A3 Homozygous/Heterozygous Splicing Mutation on the Mild Phenotype in a Family With Autosomal Recessive Alport Syndrome and a Literature Review.
Mol Genet Genomic Med
February 2025
Department of Pediatrics, The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial Children's Medical Center, Guiyang, Guizhou, China.
Background: Alport syndrome involves chronic progressive kidney failure and extrarenal organ damage caused by COL4A3, COL4A4, and COL4A5 mutations.
Methods: We initially discerned a COL4A3 splicing mutation via next-generation sequencing. Next, we used bioinformatics, renal biopsy pathology, and an in vitro minigene experiment.
A Novel Loss-of-Function Variant in COL4A3 in a Consanguineous Moroccan Family Displaying the Alport Syndrome with Variable Clinical Expression.
Mol Syndromol
February 2025
Laboratory of Human Genetics, Medical School and Pharmacy, Mohammed V University, Rabat, Morocco.
Introduction: Alport syndrome (AS) is a rare genetic disorder characterized by abnormalities in the kidneys, ears, and eyes. Its clinical presentation typically manifests in childhood or adolescence and varies widely among affected individuals, ranging from isolated hematuria to end-stage renal disease. The genetic causes of AS primarily involve mutations in the genes encoding type IV collagen , , and , which play essential roles in maintaining the structural integrity of the glomerular basement membrane in the kidney, the cochlea, and the retina.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!