ArticlePloS one2017
Alport syndrome cold cases: Missing mutations identified by exome sequencing and functional analysis.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- mRNA Sequencing to Identify Aberrant Splicing in X-linked Alport Syndrome.Kidney international reports · 2026Article
- Identification and pathogenicity analysis of a novel intronicFrontiers in medicine · 2026Article
- Pathogenic variants in the Alport genes are prevalent in the Singapore multiethnic population with highest frequency in the Chinese.Scientific reports · 2025Article
- Genetic study of Alport syndrome in Tunisia.Pediatric nephrology (Berlin, Germany) · 2025Article
- Article
- Explaining Alport syndrome-lessons from the adult nephrology clinic.Journal of rare diseases (Berlin, Germany) · 2024Review
- A Current Landscape on Alport Syndrome Cases: Characterization, Therapy and Management Perspectives.Biomedicines · 2023Review
- A Systematic Review of PathogenicKidney international reports · 2022Article
- A practical approach to the genomics of kidney disorders.Pediatric nephrology (Berlin, Germany) · 2022Review
- A disease-causing variant of COL4A5 in a Chinese family with Alport syndrome: a case series.BMC nephrology · 2021Article
- mRNA analysis identifies deep intronic variants causing Alport syndrome and overcomes the problem of negative results of exome sequencing.Scientific reports · 2021Article
- Rare genetic causes of complex kidney and urological diseases.Nature reviews. Nephrology · 2020Review
- Pathogenic evaluation of synonymous COL4A5 variants in X-linked Alport syndrome using a minigene assay.Molecular genetics & genomic medicine · 2020Article
- X-Linked Alport Syndrome in Women: Genotype and Clinical Course in 24 Cases.Frontiers in medicine · 2020Article
- Determination of the pathogenicity of known COL4A5 intronic variants by in vitro splicing assay.Scientific reports · 2019Article
- De novo mutations in COL4A5 identified by whole exome sequencing in 2 girls with Alport syndrome in Korea.Korean journal of pediatrics · 2019Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alport syndrome (AS) is an inherited progressive renal disease caused by mutations in COL4A3, COL4A4, and COL4A5 genes. Despite simultaneous screening of these genes being widely available, mutation detection still remains incomplete in a non-marginal portion of patients. Here, we applied whole-exome sequencing (WES) in 3 Italian families negative after candidate-gene analyses. In Family 1, we identified a novel heterozygous intronic variant (c.2245-40A>G) -outside the conventionally screened candidate region for diagnosis- potentially disrupting COL4A5 exon29 splicing. Using a minigene-based approach in HEK293 cells we demonstrated that this variant abolishes exon29 branch site, causing exon skipping. Moreover, skewed X-inactivation of the c.2245-40A>G allele correlated with disease severity in heterozygous females. In Family 2, WES highlighted a novel COL4A5 hemizygous missense mutation (p.Gly491Asp), which segregates with the phenotype and impacts on a highly-conserved residue. Finally, in Family 3, we detected a homozygous 24-bp in-frame deletion in COL4A3 exon1 (NM_000091.4:c.30_53del:p.Val11_Leu18del or c.40_63del24:p.Leu14_Leu21del), which is ambiguously annotated in databases, although it corresponds to a recurrent AS mutation. Functional analyses showed that this deletion disrupts COL4A3 signal peptide, possibly altering protein secretion. In conclusion, WES -together with functional studies- was fundamental for molecular diagnosis in 3 AS families, highlighting pathogenic variants that escaped previous screenings.
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