Wollnik, Bernd

[["dc.bibliographiccitation.firstpage","377"],["dc.bibliographiccitation.issue","06"],["dc.bibliographiccitation.journal","Zeitschrift für Geburtshilfe und Neonatologie"],["dc.bibliographiccitation.lastpage","380"],["dc.bibliographiccitation.volume","224"],["dc.contributor.author","Stromiedel, Helen"],["dc.contributor.author","Van Quekelberghe, Chantal"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Naimi, Ammar Al"],["dc.contributor.author","Bahlmann, Franz"],["dc.contributor.author","Sader, Robert"],["dc.contributor.author","Guchlerner, Marina"],["dc.contributor.author","Lüchtenberg, Marc"],["dc.contributor.author","Latta, Kay"],["dc.contributor.author","Cho, Chie Hee"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Kunzmann, Steffen"],["dc.date.accessioned","2021-04-14T08:23:07Z"],["dc.date.available","2021-04-14T08:23:07Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1055/a-1224-4465"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/80801"],["dc.language.iso","de"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1439-1651"],["dc.relation.issn","0948-2393"],["dc.title","Neugeborenes mit Nasenagenesie: Neonatologische Herausforderungen bei der Versorgung eines Neugeborenen mit Bosma-Arhinie-Mikrophthalmie-Syndrom (BAMS)"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","416"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Neurology"],["dc.bibliographiccitation.lastpage","419"],["dc.bibliographiccitation.volume","256"],["dc.contributor.author","Durmaz, Burak"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Cogulu, Ozgur"],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Tekgul, Hasan"],["dc.contributor.author","Hazan, Filiz"],["dc.contributor.author","Ozkinay, Ferda"],["dc.date.accessioned","2017-09-07T11:47:34Z"],["dc.date.available","2017-09-07T11:47:34Z"],["dc.date.issued","2009"],["dc.description.abstract","Pontocerebellar hypoplasia (PCH) is a heterogeneous group of disorders characterized by abnormally small cerebellum and brainstem. Recently a rare, novel form of PCH has been reported called cerebellar atrophy with progressive microcephaly (CLAM). Here we report a second family of CLAM with additional phenotypic features and novel molecular findings. Three-year old index patient had severe developmental delay and presented with short stature and microcephaly. Her cranial magnetic resonance imaging revealed hypoplasia of the cerebellum, brainstem and cerebrum associated with hypoplasia of the corpus callosum. Brainstem auditory evoked potentials revealed hearing loss and visual evoked potentials confirmed the optic atrophy. She also had seizures with two posterior epileptic foci on electroencephalogram. Molecular analysis revealed a homozygous haplotype between the markers D7S802 and D7S630 within the originally linked region, narrowing the critical region from 20 Mb to 7 Mb. Two highly relevant candidate genes, CROT and SLC25A40 located in this region were sequenced, but no causative mutations identified. Our case provides additional clinical characteristics on the previously described features of this new entity, and reducing the critical region will now allow systematic positional cloning efforts to identify the causative gene."],["dc.identifier.doi","10.1007/s00415-009-0094-0"],["dc.identifier.gro","3143145"],["dc.identifier.isi","000265732800015"],["dc.identifier.pmid","19277761"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/627"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Dr Dietrich Steinkopff Verlag"],["dc.relation.issn","0340-5354"],["dc.title","Pontocerebellar hypoplasia type III (CLAM): Extended phenotype and novel molecular findings"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","135"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","British Journal of Ophthalmology"],["dc.bibliographiccitation.lastpage","141"],["dc.bibliographiccitation.volume","92"],["dc.contributor.author","Kaplan, Y."],["dc.contributor.author","Vargel, I."],["dc.contributor.author","Kansu, T."],["dc.contributor.author","Akin, B."],["dc.contributor.author","Rohmann, E."],["dc.contributor.author","Kamaci, S."],["dc.contributor.author","Uz, E."],["dc.contributor.author","Ozcelik, T."],["dc.contributor.author","Wollnik, B."],["dc.contributor.author","Akarsu, N. A."],["dc.date.accessioned","2017-09-07T11:48:48Z"],["dc.date.available","2017-09-07T11:48:48Z"],["dc.date.issued","2008"],["dc.description.abstract","Aims: This study aimed to identify the underlying genetic defect of a large Turkish X linked nystagmus (NYS) family. Methods: Both Xp11 and Xq26 loci were tested by linkage analysis. The 12 exons and intron-exon junctions of the FRMD7 gene were screened by direct sequencing. X chromosome inactivation analysis was performed by enzymatic predigestion of DNA with a methylation-sensitive enzyme, followed by PCR of the polymorphic CAG repeat of the androgen receptor gene. Results: The family contained 162 individuals, among whom 28 had NYS. Linkage analysis confirmed the Xq26 locus. A novel missense c. 686C > G mutation, which causes the substitution of a conserved arginine at amino acid position 229 by glycine (p.R229G) in exon 8 of the FRMD7 gene, was observed. This change was not documented in 120 control individuals. The clinical findings in a female who was homozygous for the mutation were not different from those of affected heterozygous females. Skewed X inactivation was remarkable in the affected females of the family. Conclusions: A novel p. R229G mutation in the FRMD7 gene causes the NYS phenotype, and skewed X inactivation influences the manifestation of the disease in X linked NYS females."],["dc.identifier.doi","10.1136/bjo.2007.128157"],["dc.identifier.gro","3143370"],["dc.identifier.isi","000252054700031"],["dc.identifier.pmid","17962394"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/876"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0007-1161"],["dc.title","Skewed X inactivation in an X linked nystagmus family resulted from a novel, p.R229G, missense mutation in the FRMD7 gene"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e10418"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Karner, Courtney M."],["dc.contributor.author","Dietrich, M."],["dc.contributor.author","Johnson, Eric B."],["dc.contributor.author","Kappesser, Natalie"],["dc.contributor.author","Tennert, Christian"],["dc.contributor.author","Percin, E. Ferda"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Carroll, Thomas J."],["dc.contributor.author","Herz, Joachim"],["dc.date.accessioned","2017-09-07T11:46:06Z"],["dc.date.available","2017-09-07T11:46:06Z"],["dc.date.issued","2010"],["dc.description.abstract","Background: Development of the kidney is initiated when the ureteric bud (UB) branches from the Wolffian duct and invades the overlying metanephric mesenchyme (MM) triggering the mesenchymal/epithelial interactions that are the basis of organ formation. Multiple signaling pathways must be integrated to ensure proper timing and location of the ureteric bud formation. Methods and Principal Findings: We have used gene targeting to create an Lrp4 null mouse line. The mutation results in early embryonic lethality with a subpenetrant phenotype of kidney agenesis. Ureteric budding is delayed with a failure to stimulate the metanephric mesenchyme in a timely manner, resulting in failure of cellular differentiation and resulting absence of kidney formation in the mouse as well as comparable malformations in humans with Cenani-Lenz syndrome. Conclusion: Lrp4 is a multi-functional receptor implicated in the regulation of several molecular pathways, including Wnt and Bmp signaling. Lrp4(-/-) mice show a delay in ureteric bud formation that results in unilateral or bilateral kidney agenesis. These data indicate that Lrp4 is a critical regulator of UB branching and lack of Lrp4 results in congenital kidney malformations in humans and mice."],["dc.identifier.doi","10.1371/journal.pone.0010418"],["dc.identifier.gro","3142935"],["dc.identifier.isi","000277240100024"],["dc.identifier.pmid","20454682"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/394"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.title","Lrp4 Regulates Initiation of Ureteric Budding and Is Crucial for Kidney Formation - A Mouse Model for Cenani-Lenz Syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","836"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","The American Journal of Human Genetics"],["dc.bibliographiccitation.lastpage","843"],["dc.bibliographiccitation.volume","105"],["dc.contributor.author","Moosa, Shahida"],["dc.contributor.author","Yamamoto, Guilherme L."],["dc.contributor.author","Garbes, Lutz"],["dc.contributor.author","Keupp, Katharina"],["dc.contributor.author","Beleza-Meireles, Ana"],["dc.contributor.author","Moreno, Carolina Araujo"],["dc.contributor.author","Valadares, Eugenia Ribeiro"],["dc.contributor.author","de Sousa, Sérgio B."],["dc.contributor.author","Maia, Sofia"],["dc.contributor.author","Saraiva, Jorge"],["dc.contributor.author","Honjo, Rachel S."],["dc.contributor.author","Kim, Chong Ae"],["dc.contributor.author","Cabral de Menezes, Hamilton"],["dc.contributor.author","Lausch, Ekkehart"],["dc.contributor.author","Lorini, Pablo Villavicencio"],["dc.contributor.author","Lamounier, Arsonval"],["dc.contributor.author","Carniero, Tulio Canella Bezerra"],["dc.contributor.author","Giunta, Cecilia"],["dc.contributor.author","Rohrbach, Marianne"],["dc.contributor.author","Janner, Marco"],["dc.contributor.author","Semler, Oliver"],["dc.contributor.author","Beleggia, Filippo"],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Reintjes, Nadine"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Cavalcanti, Denise P."],["dc.contributor.author","Zabel, Bernhard"],["dc.contributor.author","Warman, Matthew L."],["dc.contributor.author","Bertola, Debora R."],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Netzer, Christian"],["dc.date.accessioned","2020-12-10T14:22:21Z"],["dc.date.available","2020-12-10T14:22:21Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1016/j.ajhg.2019.08.008"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/71587"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/19"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.workinggroup","RG Wollnik"],["dc.title","Autosomal-Recessive Mutations in MESD Cause Osteogenesis Imperfecta"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","123"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Journal of the Neurological Sciences"],["dc.bibliographiccitation.lastpage","130"],["dc.bibliographiccitation.volume","246"],["dc.contributor.author","Uyguner, Oya"],["dc.contributor.author","Siva, A"],["dc.contributor.author","Kayserili, Hülya"],["dc.contributor.author","Saip, S"],["dc.contributor.author","Altintas, A"],["dc.contributor.author","Apak, M. Y."],["dc.contributor.author","Albayram, S."],["dc.contributor.author","Isik, N."],["dc.contributor.author","Akman-Demir, G"],["dc.contributor.author","Tasyurekli, M"],["dc.contributor.author","Oz, B."],["dc.contributor.author","Wollnik, Bernd"],["dc.date.accessioned","2017-09-07T11:52:39Z"],["dc.date.available","2017-09-07T11:52:39Z"],["dc.date.issued","2006"],["dc.description.abstract","Mutations in Notch3 gene are responsible for the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). It is a late onset neurological disorder recognized by recurrent strokes and dementia. We describe here the clinical and molecular findings of three unrelated Turkish families with CADASIL syndrome. Two of the families were identified to have the same mutation, p.R110C (c.C328T), located in exon 3 of the Notch3 gene. Interestingly, the phenotypic expression of the disease in these two families was markedly different in severity and age of onset implicating additional genetic and/or non-genetic modulating factors involved in the pathogenesis. In addition, we identified the novel p.C201R (c.T60IC) mutation in exon 4 of the Notch3 gene in a proband of the third family with two consecutive stroke-like episodes and typical MRI findings. Mutations described here cause an odd number of cysteines in the N-terminal of the EGF domain of Notch3 protein, which seems to have an important functional effect in the pathophysiology of CADASIL. The phenotypic variability in families carrying the same molecular defect as presented here makes the prediction of prognosis inconceivable. Although DNA analysis is effective and valuable in diagnosing approximately 90% of the CADASIL patients, lack of genotype-phenotype correlation and prognostic parameters makes the presymptomatic genetic counseling very difficult. (c) 2006 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.jns.2006.02.021"],["dc.identifier.gro","3143656"],["dc.identifier.isi","000238625800019"],["dc.identifier.pmid","16730748"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1194"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","0022-510X"],["dc.title","The R110C mutation in Notch3 causes variable clinical features in two Turkish families with CADASIL syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","6903"],["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","Molecular and Cellular Biology"],["dc.bibliographiccitation.lastpage","6912"],["dc.bibliographiccitation.volume","27"],["dc.contributor.author","Shams, Imad"],["dc.contributor.author","Rohmann, Edyta"],["dc.contributor.author","Eswarakumar, Veraragavan P."],["dc.contributor.author","Lew, Erin D."],["dc.contributor.author","Yuzawa, Satoru"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Schlessinger, Joseph"],["dc.contributor.author","Lax, Irit"],["dc.date.accessioned","2017-09-07T11:49:24Z"],["dc.date.available","2017-09-07T11:49:24Z"],["dc.date.issued","2007"],["dc.description.abstract","Lacrimo-auriculo-dento-digital (LADD) syndrome is characterized by abnormalities in lacrimal and salivary glands, in teeth, and in the distal limbs. Genetic studies have implicated heterozygous mutations in fibroblast growth factor 10 (FGF10) and in FGF receptor 2 (FGFR2) in LADD syndrome. However, it is not clear whether LADD syndrome mutations (LADD mutations) are gain- or loss-of-function mutations. In order to reveal the molecular mechanism underlying LADD syndrome, we have compared the biological properties of FGF10 LADD and FGFR2 LADD mutants to the activities of their normal counterparts. These experiments show that the biological activities of three different FGF10 LADD mutants are severely impaired by different mechanisms. Moreover, haploinsufficiency caused by defective FGF10 mutants leads to LADD syndrome. We also demonstrate that the tyrosine kinase activities of FGFR2 LADD mutants expressed in transfected cells are strongly compromised. Since tyrosine kinase activity is stimulated by ligand-induced receptor dimerization, FGFR2 LADD mutants may also exert a dominant inhibitory effect on signaling via wild-type FGFR2 expressed in the same cell. These experiments underscore the importance of signal strength in mediating biological responses and that relatively small changes in receptor signaling may influence the outcome of developmental processes in cells or organs that do not possess redundant signaling pathway."],["dc.identifier.doi","10.1128/MCB.00544-07"],["dc.identifier.gro","3143431"],["dc.identifier.isi","000249642600027"],["dc.identifier.pmid","17682060"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/944"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: NIAMS NIH HHS [R01 AR051886, AR05141448, AR051886, P50 AR054086]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Amer Soc Microbiology"],["dc.relation.issn","0270-7306"],["dc.title","Lacrimo-auricuto-dento-digital syndrome is caused by reduced activity of the fibroblast growth factor 10 (FGF10)-FGF receptor 2 signaling pathwayv"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","334"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Clinical Genetics"],["dc.bibliographiccitation.lastpage","342"],["dc.bibliographiccitation.volume","90"],["dc.contributor.author","Boppudi, S."],["dc.contributor.author","Bögershausen, N."],["dc.contributor.author","Hove, H. B."],["dc.contributor.author","Percin, E. F."],["dc.contributor.author","Aslan, D."],["dc.contributor.author","Dvorsky, R."],["dc.contributor.author","Kayhan, G."],["dc.contributor.author","Li, Y."],["dc.contributor.author","Cursiefen, C."],["dc.contributor.author","Tantcheva-Poor, I."],["dc.contributor.author","Toft, P. B."],["dc.contributor.author","Bartsch, O."],["dc.contributor.author","Lissewski, C."],["dc.contributor.author","Wieland, I."],["dc.contributor.author","Jakubiczka, S."],["dc.contributor.author","Wollnik, B."],["dc.contributor.author","Ahmadian, M. R."],["dc.contributor.author","Heindl, L. M."],["dc.contributor.author","Zenker, M."],["dc.date.accessioned","2017-09-07T11:44:35Z"],["dc.date.available","2017-09-07T11:44:35Z"],["dc.date.issued","2016"],["dc.description.abstract","Oculoectodermal syndrome (OES) and encephalocraniocutaneous lipomatosis (ECCL) are rare disorders that share many common features, such as epibulbar dermoids, aplasia cutis congenita, pigmentary changes following Blaschko lines, bony tumor-like lesions, and others. About 20 cases with OES and more than 50 patients with ECCL have been reported. Both diseases were proposed to represent mosaic disorders, but only very recently whole-genome sequencing has led to the identification of somatic KRAS mutations, p.Leu19Phe and p.Gly13Asp, in affected tissue from two individuals with OES. Here we report the results of molecular genetic studies in three patients with OES and one with ECCL. In all four cases, Sanger sequencing of the KRAS gene in DNA from lesional tissue detected mutations affecting codon 146 (p.Ala146Val, p.Ala146Thr) at variable levels of mosaicism. Our findings thus corroborate the evidence of OES being a mosaic RASopathy and confirm the common etiology of OES and ECCL. KRAS codon 146 mutations, as well as the previously reported OES-associated alterations, are known oncogenic KRAS mutations with distinct functional consequences. Considering the phenotype and genotype spectrum of mosaic RASopathies, these findings suggest that the wide phenotypic variability does not only depend on the tissue distribution but also on the specific genotype."],["dc.identifier.doi","10.1111/cge.12775"],["dc.identifier.gro","3141609"],["dc.identifier.isi","000384753600005"],["dc.identifier.pmid","26970110"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/790"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1399-0004"],["dc.relation.issn","0009-9163"],["dc.title","Specific mosaic KRAS mutations affecting codon 146 cause oculoectodermal syndrome and encephalocraniocutaneous lipomatosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.contributor.author","Gönenc, Ipek Ilgin"],["dc.contributor.author","Wolff, Alexander"],["dc.contributor.author","Schmidt, Julia"],["dc.contributor.author","Zibat, Arne"],["dc.contributor.author","Müller, Christian"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Argyriou, Loukas"],["dc.contributor.author","Räschle, Markus"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Wollnik, Bernd"],["dc.date.accessioned","2022-02-23T16:37:14Z"],["dc.date.available","2022-02-23T16:37:14Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1101/2021.10.01.462717"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/100402"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/430"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.workinggroup","RG Wollnik"],["dc.title","Single-cell transcription profiles in Bloom syndrome patients link BLM deficiency with altered condensin complex expression signatures"],["dc.type","preprint"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","622"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","American journal of human genetics"],["dc.bibliographiccitation.lastpage","632"],["dc.bibliographiccitation.volume","95"],["dc.contributor.author","Hussain, Muhammad Sajid"],["dc.contributor.author","Battaglia, Agatino"],["dc.contributor.author","Szczepanski, Sandra"],["dc.contributor.author","Kaygusuz, Emrah"],["dc.contributor.author","Toliat, Mohammad Reza"],["dc.contributor.author","Sakakibara, Shin-ichi"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Nürnberg, Gudrun"],["dc.contributor.author","Moosa, Shahida"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Beleggia, Filippo"],["dc.contributor.author","Tinschert, Sigrid"],["dc.contributor.author","Clayton-Smith, Jill"],["dc.contributor.author","Vasudevan, Pradeep"],["dc.contributor.author","Urquhart, Jill E."],["dc.contributor.author","Donnai, Dian"],["dc.contributor.author","Fryer, Alan"],["dc.contributor.author","Percin, E. Ferda"],["dc.contributor.author","Brancati, Francesco"],["dc.contributor.author","Dobbie, Angus"],["dc.contributor.author","Smigiel, Robert"],["dc.contributor.author","Gillessen-Kaesbach, Gabriele"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Noegel, Angelika Anna"],["dc.contributor.author","Newman, William G."],["dc.contributor.author","Nürnberg, Peter"],["dc.date.accessioned","2017-09-07T11:45:24Z"],["dc.date.available","2017-09-07T11:45:24Z"],["dc.date.issued","2014"],["dc.description.abstract","Filippi syndrome is a rare, presumably autosomal-recessive disorder characterized by microcephaly, pre- and postnatal growth failure, syndactyly, and distinctive facial features, including a broad nasal bridge and underdeveloped alae nasi. Some affected individuals have intellectual disability, seizures, undescended testicles in males, and teeth and hair abnormalities. We performed homozygosity mapping and whole-exome sequencing in a Sardinian family with two affected children and identified a homozygous frameshift mutation, c.571dupA (p.Ile191Asnfs 6), in CKAP2L, encoding the protein cytoskeleton-associated protein 2-like (CKAP2L). The function of this protein was unknown until it was rediscovered in mice as Radmis (radial fiber and mitotic spindle) and shown to play a pivotal role in cell division of neural progenitors. Sanger sequencing of CKAP2L in a further eight unrelated individuals with clinical features consistent with Filippi syndrome revealed biallelic mutations in four subjects. In contrast to wild-type lymphoblastoid cell lines (LCLs), dividing LCLs established from the individuals homozygous for the c.571dupA mutation did not show CKAP2L at the spindle poles. Furthermore, in cells from the affected individuals, we observed an increase in the number of disorganized spindle microtubules owing to multipolar configurations and defects in chromosome segregation. The observed cellular phenotypes are in keeping with data from in vitro and in vivo knockdown studies performed in human cells and mice, respectively. Our findings show that loss-of-function mutations in CKAP2L are a major cause of Filippi syndrome."],["dc.identifier.doi","10.1016/j.ajhg.2014.10.008"],["dc.identifier.gro","3142020"],["dc.identifier.isi","000344845000013"],["dc.identifier.pmid","25439729"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/3656"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Koln Fortune; Center for Molecular Medicine Cologne"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Cell Press"],["dc.relation.eissn","1537-6605"],["dc.relation.issn","0002-9297"],["dc.title","Mutations in CKAP2L, the Human Homo log of the Mouse Radmis Gene, Cause Filippi Syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]