ArticleHuman mutation2021
A discarded synonymous variant in NPHP3 explains nephronophthisis and congenital hepatic fibrosis in several families.
Article in Human mutation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Genetic kidney diseases: Decoding molecular taxonomies to drive precision nephrology and therapeutic innovation.Genes & diseases · 2027Review
- Phenotypic and genotypic analysis of pediatric nephronophthisis patients with different levels of proteinuria.Renal failure · 2025Article
- Non-invasive screening for liver fibrosis by acoustic radiation force impulse in patients with ciliopathies.Scientific reports · 2025Article
- Cardiomyopathies in 100,000 genomes project: interval evaluation improves diagnostic yield and informs strategies for ongoing gene discovery.Genome medicine · 2024Article
- Autosomal Recessive Adolescent Syndromic Nephronophthisis Caused by a Novel Compound Heterozygous Pathogenic Variant.The American journal of case reports · 2023Article
- Splicing defects in rare diseases: transcriptomics and machine learning strategies towards genetic diagnosis.Briefings in bioinformatics · 2023Review
- [Clinical phenotype characteristics and genetic analysis in children with nephronophthisis and related syndromes caused by different gene mutations].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2023Article
- A single heterozygous nonsense mutation in the TTC21B gene causes adult-onset nephronophthisis 12: A case report and review of literature.Molecular genetics & genomic medicine · 2022Review
- Article
- Case report: A novel heterozygous synonymous variant in deep exon region ofFrontiers in genetics · 2022Article
- Article
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Authors and funding
18 authors at 9 institutions in 5 countries.
Funding
Abstract
Half of patients with a ciliopathy syndrome remain unsolved after initial analysis of whole exome sequencing (WES) data, highlighting the need for improved variant filtering and annotation. By candidate gene curation of WES data, combined with homozygosity mapping, we detected a homozygous predicted synonymous allele in NPHP3 in two children with hepatorenal fibrocystic disease from a consanguineous family. Analyses on patient-derived RNA shows activation of a cryptic mid-exon splice donor leading to frameshift. Remarkably, the same rare variant was detected in four additional families with hepatorenal disease from UK, US, and Saudi patient cohorts and in addition, another synonymous NPHP3 variant was identified in an unsolved case from the Genomics England 100,000 Genomes data set. We conclude that synonymous NPHP3 variants, not reported before and discarded by pathogenicity pipelines, solved several families with a ciliopathy syndrome. These findings prompt careful reassessment of synonymous variants, especially if they are rare and located in candidate genes.
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