ArticleGenetics in medicine : official journal of the American College of Medical Genetics2019
ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome, an ocular multisystem autosomal dominant disorder.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 63 citations in OpenAlex.
- Article
- Renal Disease in ROSAH Syndrome Masquerading as Lupus Nephritis: A Case Report and Cohort Analysis.Kidney medicine · 2026Article
- Irreversible Ocular and Systemic Damage in ROSAH Syndrome.Ophthalmology and therapy · 2026Article
- Article
- Loss of alpha-kinase 1 contributes to the formation of congenital cataracts in mice.Cellular & molecular biology letters · 2025Article
- Tocilizumab as a treatment tool for ROSAH syndrome: a case report.Journal of ophthalmic inflammation and infection · 2025Article
- Investigating the role of the ALPK1 signaling pathway in the pathogenesis of diabetic retinopathy.Scientific reports · 2025Article
- Discovery of a selective alpha-kinase 1 inhibitor for the rare genetic disease ROSAH syndrome.Nature communications · 2025Article
- The importance of ALPK1 kinase functionality as a potential biomarker for inflammatory diseases.Molecular biology reports · 2025Review
- Article
- Case Report: ROSAH syndrome presents diagnostic and therapeutic challenges.Frontiers in ophthalmology · 2025Article
- Hyperinflammation and Blindness. Screening for ROSAH Syndrome.European journal of case reports in internal medicine · 2025Article
- Article
- Measurement of the Activity of Wildtype and Disease-Causing ALPK1 Mutants in Transfected Cells With a 96-Well Format NF-κB/AP-1 Reporter Assay.Bio-protocol · 2024Article
- Quantitative Measurement of the Kinase Activity of Wildtype ALPK1 and Disease-Causing ALPK1 Mutants Using Cell-Free Radiometric Phosphorylation Assays.Bio-protocol · 2024Article
- Hallmarks of primary headache: part 1 - migraine.The journal of headache and pain · 2024Review
- Electrodiagnostic tests of the visual pathway and applications in neuro-ophthalmology.Eye (London, England) · 2024Review
- The Dawn and Advancement of the Knowledge of the Genetics of Migraine.Journal of clinical medicine · 2024Review
- Update on ocular manifestations of the main monogenic and polygenic autoinflammatory diseases.Frontiers in ophthalmology · 2024Review
- ALPK1 mutants causing ROSAH syndrome or Spiradenoma are activated by human nucleotide sugars.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
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Authors and funding
41 authors at 14 institutions in 5 countries.
Funding
Abstract
purposeTo identify the molecular cause in five unrelated families with a distinct autosomal dominant ocular systemic disorder we called ROSAH syndrome due to clinical features of retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache.
methodsIndependent discovery exome and genome sequencing in families 1, 2, and 3, and confirmation in families 4 and 5. Expression of wild-type messenger RNA and protein in human and mouse tissues and cell lines. Ciliary assays in fibroblasts from affected and unaffected family members.
resultsWe found the heterozygous missense variant in the ɑ-kinase gene, ALPK1, (c.710C>T, [p.Thr237Met]), segregated with disease in all five families. All patients shared the ROSAH phenotype with additional low-grade ocular inflammation, pancytopenia, recurrent infections, and mild renal impairment in some. ALPK1 was notably expressed in retina, retinal pigment epithelium, and optic nerve, with immunofluorescence indicating localization to the basal body of the connecting cilium of the photoreceptors, and presence in the sweat glands. Immunocytofluorescence revealed expression at the centrioles and spindle poles during metaphase, and at the base of the primary cilium. Affected family member fibroblasts demonstrated defective ciliogenesis.
conclusionHeterozygosity for ALPK1, p.Thr237Met leads to ROSAH syndrome, an autosomal dominant ocular systemic disorder.
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