{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:16:59Z","timestamp":1768436219821,"version":"3.49.0"},"reference-count":13,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,12,20]],"date-time":"2013-12-20T00:00:00Z","timestamp":1387497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:p>Loss\u2010of\u2010function mutations in <jats:italic><jats:styled-content style=\"fixed-case\">CCM1<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">KRIT1<\/jats:styled-content><\/jats:italic>, <jats:italic><jats:styled-content style=\"fixed-case\">CCM2<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">MGC4607<\/jats:styled-content><\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">CCM3<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PDCD10<\/jats:styled-content><\/jats:italic> genes are identified in the vast majority of familial cases with multiple cerebral cavernous malformations (<jats:styled-content style=\"fixed-case\">CCM<\/jats:styled-content>s). However, genomic <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> sequencing combined to large rearrangement screening fails to detect a mutation in 5% of those cases. We report a family in which <jats:styled-content style=\"fixed-case\">CCM<\/jats:styled-content> lesions were discovered fortuitously because of the investigation of a developmental delay in a boy. Three members of the family on three generations had typical multiple <jats:styled-content style=\"fixed-case\">CCM<\/jats:styled-content> lesions and no clinical signs related to <jats:styled-content style=\"fixed-case\">CCM<\/jats:styled-content>. No mutation was detected using genomic <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> sequencing and quantitative multiplex PCR of short fluorescent fragments (<jats:styled-content style=\"fixed-case\">QMPSF<\/jats:styled-content>). <jats:styled-content style=\"fixed-case\">cDNA<\/jats:styled-content> sequencing showed a 99\u2010nucleotide insertion between exons 5 and 6 of <jats:styled-content style=\"fixed-case\">CCM1<\/jats:styled-content>, resulting from a mutation located deep into intron 5 (c.262+132_262+133del) that activates a cryptic splice site. This pseudoexon leads to a premature stop codon. These data highly suggest that deep intronic mutations explain part of the incomplete mutation detection rate in <jats:styled-content style=\"fixed-case\">CCM<\/jats:styled-content> patients and underline the importance of analyzing the <jats:styled-content style=\"fixed-case\">cDNA<\/jats:styled-content> to provide comprehensive <jats:styled-content style=\"fixed-case\">CCM<\/jats:styled-content> diagnostic tests. This kind of mutation may be responsible for apparent sporadic presentations due to a reduced penetrance.<\/jats:p>","DOI":"10.1111\/cge.12322","type":"journal-article","created":{"date-parts":[[2013,11,19]],"date-time":"2013-11-19T15:07:18Z","timestamp":1384873638000},"page":"585-588","source":"Crossref","is-referenced-by-count":15,"title":["Deep intronic <scp>KRIT1<\/scp> mutation in a family with clinically silent multiple cerebral cavernous malformations"],"prefix":"10.1111","volume":"86","author":[{"given":"F.","family":"Riant","sequence":"first","affiliation":[{"name":"AP\u2010HP, Groupe Hospitalier Saint Louis, Lariboisi\u00e8re, Fernand Widal Laboratoire de G\u00e9n\u00e9tique Paris France"},{"name":"INSERM UMR\u2010S740 Paris France"},{"name":"Centre de r\u00e9f\u00e9rence pour les maladies rares des vaisseaux du cerveau et de l'\u0153il (CERVCO), INSERM U740 CHU Lariboisi\u00e8re, APHP Paris France"},{"name":"Paris Sorbonne Cit\u00e9 Universit\u00e9 Paris Diderot Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Odent","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique Clinique, CLAD Ouest, CHU Rennes CNRS UMR6290, Universit\u00e9 Rennes 1 Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Cecillon","sequence":"additional","affiliation":[{"name":"AP\u2010HP, Groupe Hospitalier Saint Louis, Lariboisi\u00e8re, Fernand Widal Laboratoire de G\u00e9n\u00e9tique Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Pasquier","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique Clinique, CLAD Ouest, CHU Rennes CNRS UMR6290, Universit\u00e9 Rennes 1 Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"de Barac\u00e9","sequence":"additional","affiliation":[{"name":"Service de N\u00e9onatologie H\u00f4pital Yves Le Foll Saint Brieuc 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