{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kozycki CT"],"funding":["National Institute of Allergy and Infectious Diseases","Intramural NIH HHS","National Eye Institute","NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH Direction","The Hill Family Fund for the Diagnosis and Management of Rare and Undiagnosed Diseases at Mass General Hospital","NHGRI NIH HHS","NIH Clinical Center","National Institute of Dental and Craniofacial Research","National Human Genome Research Institute"],"pagination":["1453-1464"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9484401"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["81(10)"],"pubmed_abstract":["Objectives
To test the hypothesis that ROSAH (retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis and headache) syndrome, caused by dominant mutation in ALPK1, is an autoinflammatory disease.Methods
This cohort study systematically evaluated 27 patients with ROSAH syndrome for inflammatory features and investigated the effect of ALPK1 mutations on immune signalling. Clinical, immunologic and radiographical examinations were performed, and 10 patients were empirically initiated on anticytokine therapy and monitored. Exome sequencing was used to identify a new pathogenic variant. Cytokine profiling, transcriptomics, immunoblotting and knock-in mice were used to assess the impact of ALPK1 mutations on protein function and immune signalling."],"journal":["Annals of the rheumatic diseases"],"pubmed_title":["Gain-of-function mutations in <i>ALPK1</i> cause an NF-κB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome."],"pmcid":["PMC9484401"],"funding_grant_id":["U01 HG007690","Z01 DE000704","Z01-DE000704","U01 HG007703","EY000477","U01HG007690"],"pubmed_authors":["Dasari S","Undiagnosed Diseases Network","Nishikomori R","Liu XZ","Yang AH","Emrick LT","Pelayo E","Jansson RW","Solem E","Gutierrez I","Novacic D","Malicdan MCV","Nehrebecky M","Worley K","Sutton S","Don Hadley SH","Cunningham M","Titah SM","Silva Alves T","Amendola L","Butte MJ","Jobanputra V","Walker M","Stoler JM","Dusser P","Jean-Marie O","Lawrence Merritt J","Bennet J","Warner BM","Bonner D","Moretti PM","Weisz-Hubshman M","Cooper CM","Loo SK","Smith EC","Coakley TR","Abu-Asab MS","Palmer CG","Fieg EL","Papp JC","Acosta MT","Sessions Cole F","Posey JE","Lanza IR","Silverman EK","Baer A","Schwartz IVD","Lee CR","Forghani I","Manna R","Dayal JG","Jarvik GP","Sobrin L","Vogel TP","Adams DR","Deardorff M","Duncan L","Krakow D","Zhao C","Byers P","Martin MG","Azamian MS","Cowen EW","Apalset EM","Bale J","Fisher PG","Fogel BL","Renteria G","Mahoney R","Sinsheimer JS","Lanpher BC","Izumi K","Scott DA","McCray AT","Tian X","Whitlock J","Newman JH","Ullah E","Chang TP","Sweetser DA","Huryn L","Ombrello AK","Koziura M","Adam M","Alvey J","Tran AA","Gochuico B","Macnamara EF","Carrasquillo O","Cobban LA","Nickerson D","Berg-Rood B","Pusey BN","Raper A","Davis J","Marth G","Cogan JD","Schaechter J","Wang LK","Kalsi S","Nicholas SK","Bivona S","Tabor HK","Bejerano G","Jarvik J","Craigen WJ","Might M","Briere L","Boyd B","Kennedy J","Isasi R","de Oliveira Poswar F","Zein W","Tucker BM","Wangler MF","Kuhns DB","Karaviti L","Pak S","Zuchner S","Wenger MW","Bayrak-Toydemir P","Hisama FM","Martin BA","Moutsopoulos N","Hayes N","Longo N","Ketkar S","Rosenfeld JA","Jamal F","Mao R","Farley G","Liu P","Sullivan K","Mamounas LA","Wallace S","Wambach J","Kone-Paut I","Esteban C","Lalani SR","Jani P","Dorrani N","Parker NH","Blue E","Saporta M","Orengo JP","Thorson W","Hammoud D","Telischi F","Wheeler MT","Hing A","Horike-Pyne M","Heller T","Martinez-Agosto JA","Mattapallil MJ","Kilich G","Caspi RR","Bamshad M","Zhang Z","Brooks BP","Tekin M","Eng CM","D'Souza P","Hom J","Kravets E","Carl Pallais J","Benneche A","Deuitch N","Nelson SF","Smith KS","LaMoure GL","Sybert V","Kodati S","Introne W","Krasnewich DM","Bohnsack J","Urv TK","Angelica D","Tifft CJ","Wan J","Long Priel D","Baldridge D","Lewis RA","Khavandgar Z","Ida H","Aksentijevich I","Holm IA","Sacco R","Kastner DL","Solnica-Krezel L","Clark GD","LeeRoyLevitt BH","Kozycki CT","Hufnagel RB","Mak BC","McCauley J","Soldatos A","Rodan LH","Byrd WE","Kohane IS","Nieves-Rodriguez S","Beck A","Perry KW","Beck D","Potocki L","Grajewski A","Crouse AB","Glass I","Wegner D","Doss AL","Ron Scott C","van Hagen PM","Verrecchia E","Shao F","Rives L","Coggins M","Sangiorgi E","Andrews A","Kiley D","Kohler JN","Shashi V","Behrens E","Tan ALM","Botto L","Ashley EA","Bacino CA","Chanprasert S","Romeo T","Eckstein DJ","Barbouth D","Briere LC","Fernandez L","Quinlan A","Zhou P","Ruzhnikov M","Maravilla K","Beggs AH","Marwaha S","Nakano-Okuno M","Huang Y","Hamid R","Zastrow DB","Reuter CM","Bellen H","Xiao C","van Wijck RTA","Dai H","Raja AN","Sisco K","Rosenzweig S","Sun A","Vanderver A","Balasubramanyam A","Burrage LC","Shin J","Beach M","Brown G","Schoch K","Wang H","Marom R","Kao-Hsieh M","Manolio TA","Toro C","Jittayasothorn Y","Pace L","Goldrich MP","Cassini T","Chao HT","Esteves C","Huang A","Oglesbee D","Yang J","Velinder M","McConkie-Rosell A","Morava E","Maduro VV","Yamamoto S","Sen N","Viskochil D","Carey J","Takada H","Sampson JB","Bademci G","Yano H","Falk M","Ben Solomon RCS","High F","Bernstein JA","Berry GT","Brenchley L","Tsai WL","Bican A","Burke EA","Brokamp E","Kobren SN","Lam B","LeBlanc K","Lam C","Rossignol F","Walley NM","Robertson AK","Hassey K","Cope H","Ward PA","Gadina M","Earl D","McGee E","MacRae CA","Mefford H","Sullivan JA","Doherty D","Mirzaa G","PhillipsIII JA","Rosenwasser N","Maas RL","Touitou I","Colley HA","Gahl WA","Loscalzo J","Schedl T","Jayadev S","Rao DA","van der Spek PJ","Dipple K","Wolfe LA","Korrick S","Raskind W","Godfrey RA","Tan QK","Westerfield M","Douine ED","Wahl CE","Golden-Grant K"],"additional_accession":[]},"is_claimable":false,"name":"Gain-of-function mutations in <i>ALPK1</i> cause an NF-κB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome.","description":"Objectives
To test the hypothesis that ROSAH (retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis and headache) syndrome, caused by dominant mutation in ALPK1, is an autoinflammatory disease.Methods
This cohort study systematically evaluated 27 patients with ROSAH syndrome for inflammatory features and investigated the effect of ALPK1 mutations on immune signalling. Clinical, immunologic and radiographical examinations were performed, and 10 patients were empirically initiated on anticytokine therapy and monitored. Exome sequencing was used to identify a new pathogenic variant. Cytokine profiling, transcriptomics, immunoblotting and knock-in mice were used to assess the impact of ALPK1 mutations on protein function and immune signalling.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Oct","modification":"2026-07-14T17:53:44.235Z","creation":"2024-11-06T07:09:15.197Z"},"accession":"S-EPMC9484401","cross_references":{"pubmed":["35868845"],"doi":["10.1136/annrheumdis-2022-222629"]}}