Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
X-linked Alport syndrome (XLAS) is a congenital renal disease caused by mutations in COL4A5. In XLAS cases suspected of being caused by aberrant splicing, transcript analysis needs to be conducted to determine splicing patterns and assess the pathogenicity. However, such analysis is not always available. We conducted a functional splicing assay using a hybrid minigene for seven COL4A5 intronic mutations: one was identified by us and six were found in the Human Gene Mutation Database. The minigene assay revealed exon skipping in four variants, exon skipping and a 10-bp insertion in one variant, and no change in one variant, which appeared not to be pathogenic. For one variant, our assay did not work. The results of all three cases for which transcript data were available were consistent with our assay results. Our findings may help to increase the accuracy of genetic test results and clarify the mechanisms causing aberrant splicing.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722096 | PMC |
| http://dx.doi.org/10.1038/s41598-019-48990-9 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Case Report: Whole genome sequencing identifies a novel deep intronic variant of uncertain significance in X-linked Alport syndrome.
Front Pediatr
August 2025
Department of Pediatrics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Diagnosing Alport syndrome can be particularly challenging when targeted sequencing methods, such as panel-based next-generation sequencing (NGS), fail to identify pathogenic variants, especially deep intronic mutations. The syndrome is caused by mutations in type IV collagen genes (, , or ), with X-linked Alport syndrome (XLAS) accounting for approximately 80% of cases. Here, we report the case of a 4-year-old boy who presented with persistent microscopic hematuria detected during routine urinalysis.
View Article and Find Full Text PDFA comprehensive splicing characterization of COL4A5 mutations and prognostic significance in a single cohort with X-linked alport syndrome.
Front Genet
June 2025
Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China.
Introduction: X-linked Alport syndrome (XLAS), caused by mutations in the COL4A5 gene, is an X-linked hereditary disease typically characterized by renal failure, hearing loss, and ocular abnormalities. It is a leading hereditary cause of end-stage renal disease (ESRD) worldwide. Studies on the genotype-phenotype correlation in Alport syndrome suggest that splicing mutations result in more severe clinical phenotypes than missense mutations.
View Article and Find Full Text PDFA novel mouse model for X-linked Alport syndrome induced by splicing mutation in the Col4a5 gene.
Sci Rep
May 2025
Department of Nephrology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China.
Alport syndrome is a hereditary kidney disease with significant variations in onset and prognosis. While 80-85% of cases are due to pathogenic variants in the COL4A5 gene, there is a notable lack of mouse models with Col4a5 mutations for basic research. Our research presents an 8-year-old child with Alport syndrome, exhibiting facial edema and abnormal urine.
View Article and Find Full Text PDF[New Genetic Variants Involved in the Pathogenesis of Autosomal Dominant Alport Syndrome: A Familial Case Report].
G Ital Nefrol
April 2025
U.O.C. Nefrologia e Dialisi Azienda Ospedaliera Cannizzaro, Catania (CT), Italy.
Alport syndrome is a hereditary disorder characterized by hematuria, proteinuria and progressive renal failure, frequently associated with extrarenal manifestations. The pathogenic variants of the COL4A5 gene are associated with X-linked Alport syndrome while those of the COL4A3 and COL4A4 genes are associated with the autosomal recessive (AR) or dominant (AD) form. The disease is characterized by considerable phenotypic variability linked to the different genes involved and the different mutations present, so the symptoms manifest themselves in different frequencies depending on the case.
View Article and Find Full Text PDF