Brain Malformations Associated With Knobloch Syndrome-Review of Literature, Expanding Clinical Spectrum, and Identification of Novel Mutations

Basit Öğe Kaydı
dc.contributor.authorCaglayan, Ahmet Okay
dc.contributor.authorBaranoski, Jacob E.
dc.contributor.authorAktar, Fesih
dc.contributor.authorHan, Wengi
dc.contributor.authorTuysuz, Beyhan
dc.contributor.authorGuzel, Asian
dc.contributor.authorGuclu, Bulent
dc.date.accessioned2024-04-24T16:15:47Z
dc.date.available2024-04-24T16:15:47Z
dc.date.issued2014
dc.departmentDicle Üniversitesien_US
dc.description.abstractBACKGROUND: Knobloch syndrome is a rare, autosomal recessive, developmental disorder characterized by stereotyped ocular abnormalities with or without occipital skull deformities (encephalocele, bone defects, and cutis aplasia). Although there is clear heterogeneity in clinical presentation, central nervous system malformations, aside from the characteristic encephalocele, have not typically been considered a component of the disease phenotype. METHODS: Four patients originally presented for genetic evaluation of symptomatic structural brain malformations. Whole-genome genotyping, whole-exome sequencing, and confirmatory Sanger sequencing were performed. Using immunohistochemical analysis, we investigated the protein expression pattern of COL18A1 in the mid-fetal and adult human cerebral cortex and then analyzed the spatial and temporal changes in the expression pattern of COL18A1 during human cortical development using the Human Brain Transcriptome database. RESULTS: We identified two novel homozygous deleterious frame-shift mutations in the COL18A1 gene. On further investigation of these patients and their families, we found that many exhibited certain characteristics of Knobloch syndrome, including pronounced ocular defects. Our data strongly support an important role for COL18A1 in brain development, and this report contributes to an enhanced characterization of the brain malformations that can result from deficiencies of collagen XVIII. CONCLUSIONS: This case series highlights the diagnostic power and clinical utility of whole-exome sequencing technology allowing clinicians and physician scientists to better understand the pathophysiology and presentations of rare diseases. We suggest that patients who are clinically diagnosed with Knobloch syndrome and/or found to have COL18A1. mutations via genetic screening should be investigated for potential structural brain abnormalities even in the absence of an encephalocele.en_US
dc.description.sponsorshipYale Program on Neurogenetics and National Institutes of Health [RC2 NS070477, U01MH081896]; Yale Center for Mendelian Disorders [U54HG006504]; Howard Hughes Medical Institute; Gregory M. Kiez and Mehmet Kutman Foundation; Scientific and Technological Research Council of Turkey [2219]en_US
dc.description.sponsorshipThe authors thank the patients and their families for participating in this study. The authors thank Angeliki Louvi, PhD for her contribution in editing the manuscript. This work was supported by the Yale Program on Neurogenetics and National Institutes of Health grants (RC2 NS070477 to M.G., U01MH081896 to N.S.), the Yale Center for Mendelian Disorders (U54HG006504 to R.P. Lifton, KG., M. Gerstein, and S. Mane), the Howard Hughes Medical Institute (to W.H.), Gregory M. Kiez and Mehmet Kutman Foundation [to M.G.], and The Scientific and Technological Research Council of Turkey [2219 to A.O.C.].en_US
dc.identifier.doi10.1016/j.pediatrneurol.2014.08.025
dc.identifier.endpage813en_US
dc.identifier.issn0887-8994
dc.identifier.issn1873-5150
dc.identifier.issue6en_US
dc.identifier.pmid25456301
dc.identifier.scopus2-s2.0-84912083992
dc.identifier.scopusqualityQ1
dc.identifier.startpage806en_US
dc.identifier.urihttps://doi.org/10.1016/j.pediatrneurol.2014.08.025
dc.identifier.urihttps://hdl.handle.net/11468/15925
dc.identifier.volume51en_US
dc.identifier.wosWOS:000346113900010
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoenen_US
dc.publisherElsevier Science Incen_US
dc.relation.ispartofPediatric Neurology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectKnobloch Syndromeen_US
dc.subjectCortical Developmenten_US
dc.subjectCol18a1en_US
dc.subjectCollagen Xviiien_US
dc.subjectWhole-Exome Sequencingen_US
dc.titleBrain Malformations Associated With Knobloch Syndrome-Review of Literature, Expanding Clinical Spectrum, and Identification of Novel Mutationsen_US
dc.titleBrain Malformations Associated With Knobloch Syndrome-Review of Literature, Expanding Clinical Spectrum, and Identification of Novel Mutations
dc.typeArticleen_US

Dosyalar

Koleksiyon

WoS İndeksli Yayınlar Koleksiyonu
PubMed İndeksli Yayın Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu