{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:41:08Z","timestamp":1772160068287,"version":"3.50.1"},"reference-count":13,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T00:00:00Z","timestamp":1614211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Cerebral cavernous malformation (CCM) is a vascular malformation of the central nervous system which may occur sporadically or segregate within families due to heterozygous variants in\n                    <jats:italic>KRIT1\/CCM1<\/jats:italic>\n                    , MGC4607\/\n                    <jats:italic>CCM2<\/jats:italic>\n                    or\n                    <jats:italic>PDCD10\/CCM3<\/jats:italic>\n                    . Intronic variants are not uncommon in familial CCM, but their clinical interpretation is often hampered by insufficient data supporting in silico predictions. Here, the mRNA analysis for two intronic unpublished variants (\n                    <jats:italic>KRIT1<\/jats:italic>\n                    c.1147\u20107\u2009T\u2009&gt;\u2009G and\n                    <jats:italic>PDCD10<\/jats:italic>\n                    c.395\u2009+\u20092 T\u2009&gt;\u2009G) and three previously published variants in\n                    <jats:italic>KRIT1<\/jats:italic>\n                    but without data supporting their effects was carried out. This study demonstrated that all variants can induce a frameshift with the lack of residues located in the C\u2010terminal regions and involved in protein\u2013protein complex formation, which is essential for vascular homeostasis. These results support the introduction of mRNA analysis in the diagnostic pathway of familial CCM and expand the knowledge of abnormal splicing patterning in this disorder.\n                  <\/jats:p>","DOI":"10.1111\/cge.13944","type":"journal-article","created":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T21:09:35Z","timestamp":1613682575000},"page":"829-835","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Improving clinical interpretation of five\n                    <scp>\n                      <i>KRIT1<\/i>\n                    <\/scp>\n                    and\n                    <scp>\n                      <i>PDCD10<\/i>\n                    <\/scp>\n                    intronic variants"],"prefix":"10.1111","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7794-6046","authenticated-orcid":false,"given":"Carmela","family":"Fusco","sequence":"first","affiliation":[{"name":"Division of Medical Genetics Fondazione IRCCS\u2010Casa Sollievo della Sofferenza  San Giovanni Rotondo Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grazia","family":"Nardella","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Fondazione IRCCS\u2010Casa Sollievo della Sofferenza  San Giovanni Rotondo Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Petracca","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Fondazione IRCCS\u2010Casa Sollievo della Sofferenza  San Giovanni Rotondo Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dario","family":"Ronchi","sequence":"additional","affiliation":[{"name":"Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico University of Milan  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Paciello","sequence":"additional","affiliation":[{"name":"Unit of Neurology Azienda Ospedaliera Regionale San Carlo  Potenza Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marilena","family":"Di Giacomo","sequence":"additional","affiliation":[{"name":"Unit of Pathology and Medical Genetics Azienda Ospedaliera Regionale San Carlo  Potenza Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Gambardella","sequence":"additional","affiliation":[{"name":"Molecular Genomics Center IRCCS Neuromed  Pozzilli Italy"},{"name":"Department of Biomolecular Sciences University of Urbino \u201cCarlo Bo\u201d  Urbino Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Lanfranconi","sequence":"additional","affiliation":[{"name":"Unit of Neurology IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Zampatti","sequence":"additional","affiliation":[{"name":"Genomic Medicine Laboratory IRCCS Fondazione Santa Lucia  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo","family":"D'Agruma","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Fondazione IRCCS\u2010Casa Sollievo della Sofferenza  San Giovanni Rotondo Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3604-194X","authenticated-orcid":false,"given":"Lucia","family":"Micale","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Fondazione IRCCS\u2010Casa Sollievo della Sofferenza  San Giovanni Rotondo Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6069-0993","authenticated-orcid":false,"given":"Marco","family":"Castori","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Fondazione IRCCS\u2010Casa Sollievo della Sofferenza  San Giovanni Rotondo 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