{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T10:18:37Z","timestamp":1768990717704,"version":"3.49.0"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T00:00:00Z","timestamp":1539734400000},"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":["81570851"],"award-info":[{"award-number":["81570851"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Ophthalmologica"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>To identify the clinical characteristics and pathogenic genes among a Chinese family with angioid streaks and to assess a novel splicing mutation at the transcriptional and translational levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Consenting family members were clinically evaluated, and blood samples were collected for targeted exome capture sequencing and\/or Sanger sequencing. The two affected siblings were assessed by multimodal fundus imaging. <jats:italic>ABCC6<\/jats:italic> splicing patterns were analysed by RNA identification and quantification using the proband's peripheral blood mononuclear cells. Minigene experiments were performed to verify the university. Plasmids expressing the transcripts were transfected into HEK293 cells to assess protein translation. Bioinformatic analyses were also performed to predict the splicing patterns and the functional consequences of the mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The two siblings were trans\u2010compound heterozygous pseudoxanthoma elasticum (PXE) patients with the same genotype (c.3703C&gt;T and c.1177\u20102A&gt;G for <jats:italic>ABCC6<\/jats:italic>) but different phenotypes. We identified several <jats:italic>ABCC6<\/jats:italic> alternative splicing transcripts that were not previously reported. The novel splicing mutation c.1177\u20102A&gt;G led to the upregulation of three transcripts, one using a cryptic splice acceptor in the upstream region of the intron, another using a cryptic splice acceptor in the downstream exon, and the third stimulating non\u2010canonical U12\u2010type splicing. All the transcripts were successfully translated <jats:italic>in\u00a0vitro<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The genotype\u2013phenotype correlation of PXE is poorly understood. The novel <jats:italic>ABCC6<\/jats:italic> splicing mutation c.1177\u20102A&gt;G results in multiple splicing patterns. Endogenous U2 to U12 conversion may occur in humans in a disease state. Peripheral blood mononuclear cells can be reliably used to study <jats:italic>ABCC6<\/jats:italic> RNA.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aos.13819","type":"journal-article","created":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T07:42:43Z","timestamp":1539762163000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Unexpected ABCC6 mRNA splicing in a Chinese family with pseudoxanthoma elasticum"],"prefix":"10.1111","volume":"97","author":[{"given":"Qiao","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Shanghai General Hospital Shanghai Jiao Tong University Shanghai China"},{"name":"Shanghai Key Laboratory of Fundus Disease Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weijun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Shanghai General Hospital Shanghai Jiao Tong University Shanghai China"},{"name":"Shanghai Key Laboratory of Fundus Disease Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lifang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Cell Biology Shanghai Key Laboratory of Tumor Microenvironment and Inflammation Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Shanghai General Hospital Shanghai Jiao Tong University Shanghai China"},{"name":"Shanghai Key Laboratory of Fundus Disease Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuemei","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Cell Biology Shanghai Key Laboratory of Tumor Microenvironment and Inflammation Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4246-4343","authenticated-orcid":false,"given":"Xun","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Shanghai General Hospital Shanghai Jiao Tong University Shanghai China"},{"name":"Shanghai Key Laboratory of Fundus Disease Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,10,17]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.1.30"},{"key":"e_1_2_5_4_1","first-page":"912478","article-title":"Identification of a new splice variant of the human ABCC6 transporter","volume":"2008","author":"Armentano MF","year":"2008","journal-title":"Biochem Res Int"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2013.10.016"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1745-6150-3-19"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/76109"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2007.08076.x"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80292-0"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.5654.1"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.030171"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp215"},{"key":"e_1_2_5_13_1","first-page":"81","article-title":"Angioid streaks, clinical course, complications, and current therapeutic management","volume":"5","author":"Georgalas I","year":"2009","journal-title":"Ther Clin Risk Manag"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.38.7.457"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.16-19388"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.185.4154.862"},{"key":"e_1_2_5_17_1","first-page":"309","article-title":"Understanding angioid streaks","volume":"68","author":"Gurwood AS","year":"1997","journal-title":"J Am Optom Assoc"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/aos.12262"},{"key":"e_1_2_5_19_1","first-page":"299","article-title":"Angioid streaks. 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