ArticleAmerican journal of human genetics2013
Mutations in SPAG1 cause primary ciliary dyskinesia associated with defective outer and inner dynein arms.
Article in American journal of human genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00807482 (Diagnostic and Clinical Characterization of Patients With Unusual Genetic Disorders of the Airways), which is not on this map. Cited by 86 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Diagnostic and Clinical Characterization of Patients With Unusual Genetic Disorders of the Airways
Who cites it
86 citing papers in PubMed, 2 syntheses or guidelines pooled it, 145 citations in OpenAlex.
- European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia.The European respiratory journal · 2017Guideline
- Diagnosis, monitoring, and treatment of primary ciliary dyskinesia: PCD foundation consensus recommendations based on state of the art review.Pediatric pulmonology · 2016Guideline
- DNAAF19-RUVBL1/2 complex recruits multiple adaptors to promote dynein arm assembly.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A Novel Frameshift Variant in SPAG1 Likely Causes Primary Ciliary Dyskinesia in Cocker Spaniels in Australia.Animal genetics · 2026Article
- An integrative structural biology approach reveals the dynamic organization of the R2SP quaternary chaperone complex.Nature communications · 2026Article
- Proteomic Exploration of L1CAMInternational journal of molecular sciences · 2025Article
- Renal transcriptome-wide analyses in association with kidney black carbon load.Particle and fibre toxicology · 2025Article
- The lack of homozygotes with a large deletion encompassingGenes & diseases · 2025Article
- DynAPs and cytoplasmic assembly of axonemal dyneins.Journal of cell science · 2025Article
- Promoter Deletion Leading to Allele Specific Expression in a Genetically Unsolved Case of Primary Ciliary Dyskinesia.American journal of medical genetics. Part A · 2025Article
- Primary ciliary dyskinesia as a rare cause of male infertility: case report and literature overview.Basic and clinical andrology · 2024Article
- Inherently disordered regions of axonemal dynein assembly factors.Cytoskeleton (Hoboken, N.J.) · 2024Review
- Analysis of clinical characteristics and histopathological transcription in 40 patients afflicted by epilepsy stemming from focal cortical dysplasia.Epilepsia open · 2024Article
- Functions of cilia in cardiac development and disease.Annals of human genetics · 2024Review
- Review
- FBB18 participates in preassembly of almost all axonemal dyneins independent of R2TP complex.PLoS genetics · 2022Article
- The Role of Hsp90-R2TP in Macromolecular Complex Assembly and Stabilization.Biomolecules · 2022Review
- Autosomal Dominant Retinitis Pigmentosa-Associated TOPORS Protein Truncating Variants Are Exclusively Located in the Region of Amino Acid Residues 807 to 867.Investigative ophthalmology & visual science · 2022Article
- A change of heart: new roles for cilia in cardiac development and disease.Nature reviews. Cardiology · 2022Review
- The role of SPAG1 in the assembly of axonemal dyneins in human airway epithelia.Journal of cell science · 2022Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
41 authors at 9 institutions in 3 countries.
Funding
Abstract
Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, autosomal-recessive disorder, characterized by oto-sino-pulmonary disease and situs abnormalities. PCD-causing mutations have been identified in 20 genes, but collectively they account for only ∼65% of all PCDs. To identify mutations in additional genes that cause PCD, we performed exome sequencing on three unrelated probands with ciliary outer and inner dynein arm (ODA+IDA) defects. Mutations in SPAG1 were identified in one family with three affected siblings. Further screening of SPAG1 in 98 unrelated affected individuals (62 with ODA+IDA defects, 35 with ODA defects, 1 without available ciliary ultrastructure) revealed biallelic loss-of-function mutations in 11 additional individuals (including one sib-pair). All 14 affected individuals with SPAG1 mutations had a characteristic PCD phenotype, including 8 with situs abnormalities. Additionally, all individuals with mutations who had defined ciliary ultrastructure had ODA+IDA defects. SPAG1 was present in human airway epithelial cell lysates but was not present in isolated axonemes, and immunofluorescence staining showed an absence of ODA and IDA proteins in cilia from an affected individual, thus indicating that SPAG1 probably plays a role in the cytoplasmic assembly and/or trafficking of the axonemal dynein arms. Zebrafish morpholino studies of spag1 produced cilia-related phenotypes previously reported for PCD-causing mutations in genes encoding cytoplasmic proteins. Together, these results demonstrate that mutations in SPAG1 cause PCD with ciliary ODA+IDA defects and that exome sequencing is useful to identify genetic causes of heterogeneous recessive disorders.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.