{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T04:22:21Z","timestamp":1784953341996,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,4,22]],"date-time":"2019-04-22T00:00:00Z","timestamp":1555891200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81522014"],"award-info":[{"award-number":["81522014"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31771390"],"award-info":[{"award-number":["31771390"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LD18H120001LD"],"award-info":[{"award-number":["LD18H120001LD"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Adenosine diphosphate (ADP)\u2010ribosylation factor\u2010like 2 (ARL2) protein participates in a broad range of cellular processes and acts as a mediator for mutant ARL2BP in cilium\u2010associated retinitis pigmentosa and for mutant HRG4 in mitochondria\u2010related photoreceptor degeneration. However, mutant ARL2 has not been linked to any human disease so far. Here, we identified a de novo variant in\n                    <jats:italic>ARL2<\/jats:italic>\n                    (c.44G\u2009&gt;\u2009T, p.R15L) in a Chinese pedigree with MRCS (microcornea, rod\u2010cone dystrophy, cataract, and posterior staphyloma) syndrome through whole\u2010exome sequencing and co\u2010segregation analysis. Co\u2010immunoprecipitation assay and immunoblotting confirmed that the mutant ARL2 protein showed a 62% lower binding affinity for HRG4 while a merely 18% lower binding affinity for ARL2BP. Immunofluorescence images of ARL2 and HRG4 co\u2010localizing with cytochrome c in HeLa cells described their relationship with mitochondria. Further analyses of the mitochondrial respiratory chain and adenosine triphosphate production showed significant abnormalities under an\n                    <jats:italic>ARL2<\/jats:italic>\n                    \u2010mutant condition. Finally, we generated transgenic mice to test the pathogenicity of this variant and observed retinal degeneration complicated with microcornea and cataract that were similar to those in our patients. In conclusion, we uncover\n                    <jats:italic>ARL2<\/jats:italic>\n                    as a novel candidate gene for MRCS syndrome and suggest a mitochondria\u2010related mechanism of the first\n                    <jats:italic>ARL2<\/jats:italic>\n                    variant through site\u2010directed mutagenesis studies.\n                  <\/jats:p>","DOI":"10.1111\/cge.13541","type":"journal-article","created":{"date-parts":[[2019,4,4]],"date-time":"2019-04-04T02:49:04Z","timestamp":1554346144000},"page":"61-71","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Whole\u2010exome sequencing identified\n                    <i>ARL2<\/i>\n                    as a novel candidate gene for MRCS (microcornea, rod\u2010cone dystrophy, cataract, and posterior staphyloma) syndrome"],"prefix":"10.1111","volume":"96","author":[{"given":"Xue\u2010Bi","family":"Cai","sequence":"first","affiliation":[{"name":"Lab for Stem Cell and Retinal Regeneration, Institute of Stem Cell Research; Division of Ophthalmic Genetics, The Eye Hospital Wenzhou Medical University  Wenzhou China"},{"name":"State Key Laboratory of Ophthalmology, Optometry and Vision Science Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun\u2010Chao","family":"Wu","sequence":"additional","affiliation":[{"name":"Lab for Stem Cell and Retinal Regeneration, Institute of Stem Cell Research; Division of Ophthalmic Genetics, The Eye Hospital Wenzhou Medical University  Wenzhou China"},{"name":"State Key Laboratory of Ophthalmology, Optometry and Vision Science Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Lab for Stem Cell and Retinal Regeneration, Institute of Stem Cell Research; Division of Ophthalmic Genetics, The Eye Hospital Wenzhou Medical 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Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lue","family":"Xiang","sequence":"additional","affiliation":[{"name":"Lab for Stem Cell and Retinal Regeneration, Institute of Stem Cell Research; Division of Ophthalmic Genetics, The Eye Hospital Wenzhou Medical University  Wenzhou China"},{"name":"State Key Laboratory of Ophthalmology, Optometry and Vision Science Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Optometry and Vision Science Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu\u2010Feng","family":"Huang","sequence":"additional","affiliation":[{"name":"Lab for Stem Cell and Retinal Regeneration, Institute of Stem Cell Research; Division of Ophthalmic Genetics, The Eye Hospital Wenzhou Medical University  Wenzhou China"},{"name":"State Key Laboratory of Ophthalmology, Optometry and Vision Science Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deng","family":"Pan","sequence":"additional","affiliation":[{"name":"Lab for Stem Cell and Retinal Regeneration, Institute of Stem Cell Research; Division of Ophthalmic Genetics, The Eye Hospital Wenzhou Medical University  Wenzhou China"},{"name":"State Key Laboratory of Ophthalmology, Optometry and Vision Science Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Lu","sequence":"additional","affiliation":[{"name":"Protein Quality Control and Diseases Laboratory, Institute of Biophysics, School of Life Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, 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