{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:51:34Z","timestamp":1790175094663,"version":"4.1.0"},"reference-count":16,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,4,29]],"date-time":"2016-04-29T00:00:00Z","timestamp":1461888000000},"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":[[2016,12]]},"abstract":"<jats:p>Pontocerebellar hypoplasias (<jats:styled-content style=\"fixed-case\">PCH<\/jats:styled-content>) are characterized by lack of development and\/or early neurodegeneration of cerebellum and brainstem. We report five patients referred for <jats:styled-content style=\"fixed-case\">PCH<\/jats:styled-content>, showing atypical clinical and magnetic resonance imaging (<jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>) features suggestive of defects in the Reelin pathway. We screened for mutations in <jats:italic><jats:styled-content style=\"fixed-case\">RELN<\/jats:styled-content><\/jats:italic> or <jats:italic><jats:styled-content style=\"fixed-case\">VLDLR<\/jats:styled-content><\/jats:italic> and compared the phenotype of these patients with that of previously reported patients. All patients had profound cerebellar hypoplasia on <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content> with peculiar cerebellar morphology, associated with flattened pons and neocortical abnormalities. Patient 1 had profound motor and intellectual disability with moderate lissencephaly suggestive of <jats:italic><jats:styled-content style=\"fixed-case\">RELN<\/jats:styled-content><\/jats:italic> mutations and was shown to harbor a splicing homozygous <jats:italic><jats:styled-content style=\"fixed-case\">RELN<\/jats:styled-content><\/jats:italic> mutation. The four other patients had a milder phenotype consistent with <jats:styled-content style=\"fixed-case\">CARMQ1<\/jats:styled-content> (cerebellar ataxia and mental retardation with or without quadrupedal locomotion). These patients showed mild simplification or thickening of cortical gyration and had <jats:italic><jats:styled-content style=\"fixed-case\">VLDLR<\/jats:styled-content><\/jats:italic> mutations. Reelin signaling regulates neuronal migration in the developing mammalian brain. <jats:styled-content style=\"fixed-case\">VLDLR<\/jats:styled-content> is a key component of the Reelin pathway. Our patients had a very small and dysplatic cerebellar vermis that should suggest the involvement of these genes. Moreover, differences in clinical severity, involvement of the cerebellar hemispheres, together with the severity of the neocortical defect, enables <jats:italic><jats:styled-content style=\"fixed-case\">RELN<\/jats:styled-content><\/jats:italic>\u2010mutated patients to be distinguished from <jats:italic><jats:styled-content style=\"fixed-case\">VLDLR<\/jats:styled-content><\/jats:italic>\u2010mutated patients.<\/jats:p>","DOI":"10.1111\/cge.12779","type":"journal-article","created":{"date-parts":[[2016,3,22]],"date-time":"2016-03-22T12:27:25Z","timestamp":1458649645000},"page":"545-549","source":"Crossref","is-referenced-by-count":45,"title":["<i><scp>RELN<\/scp><\/i> and <i><scp>VLDLR<\/scp><\/i> mutations underlie two distinguishable clinico\u2010radiological phenotypes"],"prefix":"10.1111","volume":"90","author":[{"given":"S.","family":"Valence","sequence":"first","affiliation":[{"name":"APHP, GHUEP, H\u00f4pital Armand Trousseau Centre de R\u00e9f\u00e9rence \u2018Malformations et maladies cong\u00e9nitales du cervelet\u2019  Paris France"},{"name":"APHP, GHUEP, H\u00f4pital Armand\u2010Trousseau Service de Neurop\u00e9diatrie  Paris France"},{"name":"Sorbonne Universit\u00e9s, UPMC Universit\u00e9 Paris 06 GRC-UPMC ConCer-LD  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Garel","sequence":"additional","affiliation":[{"name":"APHP, GHUEP, H\u00f4pital Armand Trousseau Centre de R\u00e9f\u00e9rence \u2018Malformations et maladies cong\u00e9nitales du cervelet\u2019  Paris France"},{"name":"APHP, GHUEP, H\u00f4pital Armand\u2010Trousseau Service de Radiologie  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Barth","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique CHU d'Angers  Angers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Toutain","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique, CHU de Tours, and UMR_INSERM U930, Facult\u00e9 de M\u00e9decine Universit\u00e9 Fran\u00e7ois Rabelais  Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Paris","sequence":"additional","affiliation":[{"name":"Service de Neurologie P\u00e9diatrique CHU J Minjoz  Besan\u00e7on France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Amsallem","sequence":"additional","affiliation":[{"name":"Service de Neurologie P\u00e9diatrique CHU J Minjoz  Besan\u00e7on France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.\u2010A.","family":"Barthez","sequence":"additional","affiliation":[{"name":"Service de Neurologie P\u00e9diatrique CHU de Tours  Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Mayer","sequence":"additional","affiliation":[{"name":"APHP, GHUEP, H\u00f4pital Armand\u2010Trousseau Service de Neurop\u00e9diatrie  Paris 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,4,29]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70024-3"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31403"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0387-7604(93)90080-R"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-6-50"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.07.005"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.02.058"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-7-18"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31402"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/79246"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.02.005"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2010.07222.x"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31667"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.04.020"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073809332696"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1086\/444400"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-19120"}],"container-title":["Clinical 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