{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T12:38:35Z","timestamp":1740141515970,"version":"3.37.3"},"reference-count":18,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,4,4]],"date-time":"2017-04-04T00:00:00Z","timestamp":1491264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:sec><jats:label\/><jats:p>Among more than 5,000 human monogenic disorders with known causative genes, transposable element insertion of a Long Interspersed Nuclear Element 1 (LINE1, L1) is known as the mechanistic basis in only 13 genetic conditions. Meckel\u2013Gruber syndrome is a rare ciliopathy characterized by occipital encephalocele and cystic kidney disease. Here, we document a boy with occipital encephalocele, post\u2010axial polydactyly, and multicystic renal disease. A medical exome analysis detected a heterozygous frameshift mutation, c.4582_4583delCG p.(Arg1528Serfs*17) in <jats:italic>CC2D2A<\/jats:italic> in the maternally derived allele. The further use of a dedicated bioinformatics algorithm for detecting retrotransposon insertions led to the detection of an L1 insertion affecting exon 7 in the paternally derived allele. The complete sequencing and sequence homology analysis of the inserted L1 element showed that the L1 element was classified as L1HS (L1 human specific) and that the element had intact open reading frames in the two L1\u2010encoded proteins. This observation ranks Meckel\u2013Gruber syndrome as only the 14th disorder to be caused by an L1 insertion among more than 5,000 known human genetic disorders. Although a transposable element detection algorithm is not included in the current best\u2010practice next\u2010generation sequencing analysis, the present observation illustrates the utility of such an algorithm, which would require modest computational time and resources. Whether the seemingly infrequent recognition of L1 insertion in the pathogenesis of human genetic diseases might simply reflect a lack of appropriate detection methods remains to be seen.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38167","type":"journal-article","created":{"date-parts":[[2017,4,5]],"date-time":"2017-04-05T16:42:24Z","timestamp":1491410544000},"page":"1353-1357","source":"Crossref","is-referenced-by-count":10,"title":["Diagnostic use of computational retrotransposon detection: Successful definition of pathogenetic mechanism in a ciliopathy phenotype"],"prefix":"10.1002","volume":"173","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7311-4135","authenticated-orcid":false,"given":"Toshiki","family":"Takenouchi","sequence":"first","affiliation":[{"name":"Center for Medical Genetics Keio University School of Medicine Tokyo Japan"},{"name":"Department of Pediatrics Keio University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomu","family":"Kuchikata","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Tokyo Metropolitan Children's Medical Center Fuchu Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Yoshihashi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Tokyo Metropolitan Children's Medical Center Fuchu Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mineko","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Keio University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoko","family":"Uehara","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Keio University School of Medicine Tokyo 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