Wollnik, Bernd

[["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","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"]]

[["dc.bibliographiccitation.firstpage","728"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","American Journal of Medical Genetics"],["dc.bibliographiccitation.lastpage","733"],["dc.bibliographiccitation.volume","170"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Wieczorek, Dagmar"],["dc.contributor.author","Boegershausen, Nina"],["dc.contributor.author","Beleggia, Filippo"],["dc.contributor.author","Moeller-Hartmann, Claudia"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Wollnik, Bernd"],["dc.date.accessioned","2017-09-07T11:54:36Z"],["dc.date.available","2017-09-07T11:54:36Z"],["dc.date.issued","2016"],["dc.description.abstract","Using whole-exome sequencing, we identified a homozygous acceptor splice-site mutation in intron 6 of the KATNB1 gene in a patient from a consanguineous Turkish family who presented with congenital microcephaly, lissencephaly, short stature, polysyndactyly, and dental abnormalities. cDNA analysis revealed complete loss of the natural acceptor splice-site resulting either in the usage of an alternative, exonic acceptor splice-site inducing a frame-shift and premature protein truncation or, to a minor extent, in complete skipping of exon 7. Both effects most likely lead to complete loss of KATNB1 function. Homozygous and compound heterozygous mutations in KATNB1 have very recently been described as a cause of microcephaly with brain malformations and seizures. We extend the KATNB1 associated phenotype by describing a syndrome characterized by primordial dwarfism, lissencephaly, polysyndactyly, and dental anomalies, which is caused by a homozygous truncating KATNB1 mutation. (c) 2015 Wiley Periodicals, Inc."],["dc.identifier.doi","10.1002/ajmg.a.37484"],["dc.identifier.gro","3141719"],["dc.identifier.isi","000373098900028"],["dc.identifier.pmid","26640080"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/313"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley-blackwell"],["dc.relation.eissn","1552-4833"],["dc.relation.issn","1552-4825"],["dc.title","A Syndrome of Microcephaly, Short Stature, Polysyndactyly, and Dental Anomalies Caused by a Homozygous KATNB1 Mutation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","919"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","American journal of human genetics"],["dc.bibliographiccitation.lastpage","927"],["dc.bibliographiccitation.volume","91"],["dc.contributor.author","von Ameln, Simon"],["dc.contributor.author","Wang, Geng"],["dc.contributor.author","Boulouiz, Redouane"],["dc.contributor.author","Rutherford, Mark A."],["dc.contributor.author","Smith, Geoffrey M."],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Pogoda, Hans-Martin"],["dc.contributor.author","Nürnberg, Gudrun"],["dc.contributor.author","Stiller, Barbara"],["dc.contributor.author","Volk, Alexander E."],["dc.contributor.author","Borck, Guntram"],["dc.contributor.author","Hong, Jason S."],["dc.contributor.author","Goodyear, Richard J."],["dc.contributor.author","Abidi, Omar"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Hofmann, Kay"],["dc.contributor.author","Richardson, Gu Y. P."],["dc.contributor.author","Hammerschmidt, Matthias"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Koehler, Carla M."],["dc.contributor.author","Teitell, Michael A."],["dc.contributor.author","Barakat, Abdelhamid"],["dc.contributor.author","Kubisch, Christian"],["dc.date.accessioned","2017-09-07T11:48:21Z"],["dc.date.available","2017-09-07T11:48:21Z"],["dc.date.issued","2012"],["dc.description.abstract","A subset of nuclear-encoded RNAs has to be imported into mitochondria for the proper replication and transcription of the mitochondrial genome and, hence, for proper mitochondrial function. Polynucleotide phosphorylase (PNPase or PNPT1) is one of the very few components known to be involved in this poorly characterized process in mammals. At the organismal level, however, the effect of PNPase dysfunction and impaired mitochondrial RNA import are unknown. By positional cloning, we identified a homozygous PNPT1 missense mutation (c.1424A>G predicting the protein substitution p.Glu475Gly) of a highly conserved PNPase residue within the second RNase-PH domain in a family affected by autosomal-recessive nonsyndromic hearing impairment. In vitro analyses in bacteria, yeast, and mammalian cells showed that the identified mutation results in a hypofunctional protein leading to disturbed PNPase trimerization and impaired mitochondrial RNA import. Immunohistochemistry revealed strong PNPase staining in the murine cochlea, including the sensory hair cells and the auditory ganglion neurons. In summary, we show that a component of the mitochondrial RNA-import machinery is specifically required for auditory function."],["dc.identifier.doi","10.1016/j.ajhg.2012.09.002"],["dc.identifier.gro","3142441"],["dc.identifier.isi","000311011400015"],["dc.identifier.pmid","23084290"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8318"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Cell Press"],["dc.relation.issn","0002-9297"],["dc.title","A Mutation in PNPT1, Encoding Mitochondrial-RNA-Import Protein PNPase, Causes Hereditary Hearing Loss"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1113"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Nature Genetics"],["dc.bibliographiccitation.lastpage","1118"],["dc.bibliographiccitation.volume","40"],["dc.contributor.author","Budde, Birgit"],["dc.contributor.author","Namavar, Yasmin"],["dc.contributor.author","Barth, Peter G."],["dc.contributor.author","Poll-The, Bwee Tien"],["dc.contributor.author","Nürnberg, Gudrun"],["dc.contributor.author","Becker, Christian"],["dc.contributor.author","van Ruissen, Fred"],["dc.contributor.author","Weterman, Marian A. J."],["dc.contributor.author","Fluiter, Kees"],["dc.contributor.author","Beek, Erik T. te"],["dc.contributor.author","Aronica, Eleonora"],["dc.contributor.author","van der Knaap, Marjo S."],["dc.contributor.author","Hoehne, Wolfgang"],["dc.contributor.author","Toliat, Mohammad Reza"],["dc.contributor.author","Crow, Yanick J."],["dc.contributor.author","Steinlin, Maja"],["dc.contributor.author","Voit, Thomas"],["dc.contributor.author","Roelens, Filip"],["dc.contributor.author","Brussel, Wim"],["dc.contributor.author","Brockmann, Knut"],["dc.contributor.author","Kyllerman, Marten"],["dc.contributor.author","Boltshauser, Eugen"],["dc.contributor.author","Hammersen, Gerhard"],["dc.contributor.author","Willemsen, Michel"],["dc.contributor.author","Basel-Vanagaite, Lina"],["dc.contributor.author","Kraegeloh-Mann, Ingeborg"],["dc.contributor.author","Vries, Linda S. de"],["dc.contributor.author","Sztriha, Laszlo"],["dc.contributor.author","Muntoni, Francesco"],["dc.contributor.author","Ferrie, Colin D."],["dc.contributor.author","Battini, Roberta"],["dc.contributor.author","Hennekam, Raoul C. M."],["dc.contributor.author","Grillo, Eugenio"],["dc.contributor.author","Beemer, Frits A."],["dc.contributor.author","Stoets, Loes M. E."],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Baas, Frank"],["dc.date.accessioned","2017-09-07T11:48:13Z"],["dc.date.available","2017-09-07T11:48:13Z"],["dc.date.issued","2008"],["dc.description.abstract","Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological disorders."],["dc.identifier.doi","10.1038/ng.204"],["dc.identifier.gro","3143250"],["dc.identifier.isi","000258761200026"],["dc.identifier.pmid","18711368"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/743"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1061-4036"],["dc.title","tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","580"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Molecular Genetics & Genomic Medicine"],["dc.bibliographiccitation.lastpage","584"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Moosa, Shahida"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Lyngbye, Troels"],["dc.contributor.author","Christensen, Rikke"],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Vogel, Ida"],["dc.contributor.author","Wollnik, Bernd"],["dc.date.accessioned","2018-04-23T11:49:11Z"],["dc.date.available","2018-04-23T11:49:11Z"],["dc.date.issued","2017"],["dc.description.abstract","Background Very recently, compound heterozygous loss‐of‐function mutations in TELO2 were shown to underlie the newly‐described You‐Hoover‐Fong syndrome. TELO2 forms part of the co‐chaperone triple T complex (TTT complex), which plays an important role in the maturation and stabilization of the phosphatidylinositol 3‐kinase‐related protein kinases (PIKKs). Patients with mutations in TELO2 present with microcephaly and associated intellectual disability, postnatal growth retardation and dysmorphic features. Here, we describe Danish sisters with two novel mutations in TELO2. In particular, we highlight the clinical features of the 22‐year index patient, which are more severe than the original patients described, thereby expanding the clinical spectrum of YHFS. Methods The index patient was clinically examined and subsequently exome sequencing on her DNA was performed using the NimbleGen SeqCap EZ Human Exome Library v2.0 enrichment kit on an Illumina HiSeq2000 sequencer. Results Two novel, compound heterozygous mutations in TELO2 were identified in the index patient and her deceased older sister. Both have clinical features in keeping with the original YHFS patients, although the index patient seems to represent the severe end of the clinical spectrum with very marked prenatal onset growth retardation and microcephaly, severe global developmental delay and facial dysmorphic features. Additional clinical findings include eye anomalies (bilateral congenital cataracts, retinitis pigmentosa, convergent squint), bilateral conductive hearing loss, an abnormal kidney and seizures. Conclusion This report of Danish siblings with YHFS serves to expand the presentation of this new syndrome to include features in keeping with a form of microcephalic primordial dwarfism on the severe end of the clinical spectrum, and adds two novel mutations to the TELO2 mutational spectrum."],["dc.identifier.doi","10.1002/mgg3.287"],["dc.identifier.gro","3142502"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13656"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","2324-9269"],["dc.title","Novel compound heterozygous mutations in TELO2 in a patient with severe expression of You-Hoover-Fong syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","American Journal of Medical Genetics Part A"],["dc.bibliographiccitation.volume","170"],["dc.contributor.author","Moosa, Shahida"],["dc.contributor.author","Fano, Virginia"],["dc.contributor.author","Obregon, Maria Gabriela"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Nishimura, Gen"],["dc.contributor.author","Wollnik, Bernd"],["dc.date.accessioned","2017-09-07T11:54:27Z"],["dc.date.available","2017-09-07T11:54:27Z"],["dc.date.issued","2016"],["dc.identifier.doi","10.1002/ajmg.a.37884"],["dc.identifier.gro","3145170"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2876"],["dc.notes.intern","Crossref Import"],["dc.notes.status","public"],["dc.publisher","Wiley-Blackwell"],["dc.relation.issn","1552-4825"],["dc.title","Cover Image, Volume 170A, Number 9, September 2016"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1216"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","American Journal of Medical Genetics Part A"],["dc.bibliographiccitation.lastpage","1221"],["dc.bibliographiccitation.volume","185"],["dc.contributor.author","Gangfuß, Andrea"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Czeschik, Johanna Christina"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Bögershausen, Nina"],["dc.contributor.author","Burfeind, Peter"],["dc.contributor.author","Wieczorek, Dagmar"],["dc.contributor.author","Kaiser, Frank"],["dc.contributor.author","Roos, Andreas"],["dc.contributor.author","Kölbel, Heike"],["dc.contributor.author","Schara‐Schmidt, Ulrike"],["dc.contributor.author","Kuechler, Alma"],["dc.date.accessioned","2021-04-14T08:30:46Z"],["dc.date.available","2021-04-14T08:30:46Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1002/ajmg.a.62070"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83369"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1552-4833"],["dc.relation.issn","1552-4825"],["dc.title","Intellectual disability associated with craniofacial dysmorphism, cleft palate, and congenital heart defect due to a de novo MEIS2 mutation: A clinical longitudinal study"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","467"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Molecular Genetics & Genomic Medicine"],["dc.bibliographiccitation.lastpage","480"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Brown, Karen E."],["dc.contributor.author","Kayserili, Hülya"],["dc.contributor.author","Pohl, Esther"],["dc.contributor.author","Caliebe, Almuth"],["dc.contributor.author","Zahnleiter, Diana"],["dc.contributor.author","Rosser, Elisabeth"],["dc.contributor.author","Bögershausen, Nina"],["dc.contributor.author","Uyguner, Oya"],["dc.contributor.author","Altunoglu, Umut"],["dc.contributor.author","Nürnberg, Gudrun"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Rauch, Anita"],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Thiel, Christian Thomas"],["dc.contributor.author","Wollnik, Bernd"],["dc.date.accessioned","2017-09-07T11:54:27Z"],["dc.date.available","2017-09-07T11:54:27Z"],["dc.date.issued","2015"],["dc.description.abstract","Seckel syndrome is a heterogeneous, autosomal recessive disorder marked by prenatal proportionate short stature, severe microcephaly, intellectual disability, and characteristic facial features. Here, we describe the novel homozygous splice‐site mutations c.383+1G>C and c.4005‐9A>G in CDK5RAP2 in two consanguineous families with Seckel syndrome. CDK5RAP2 (CEP215) encodes a centrosomal protein which is known to be essential for centrosomal cohesion and proper spindle formation and has been shown to be causally involved in autosomal recessive primary microcephaly. We establish CDK5RAP2 as a disease‐causing gene for Seckel syndrome and show that loss of functional CDK5RAP2 leads to severe defects in mitosis and spindle organization, resulting in cells with abnormal nuclei and centrosomal pattern, which underlines the important role of centrosomal and mitotic proteins in the pathogenesis of the disease. Additionally, we present an intriguing case of possible digenic inheritance in Seckel syndrome: A severely affected child of nonconsanguineous German parents was found to carry heterozygous mutations in CDK5RAP2 and CEP152. This finding points toward a potential additive genetic effect of mutations in CDK5RAP2 and CEP152."],["dc.identifier.doi","10.1002/mgg3.158"],["dc.identifier.gro","3145172"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2878"],["dc.language.iso","en"],["dc.notes.intern","Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","2324-9269"],["dc.title","Mutations in CDK5RAP2 cause Seckel syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","36"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Genetics"],["dc.bibliographiccitation.lastpage","+"],["dc.bibliographiccitation.volume","48"],["dc.contributor.author","Harley, Margaret E."],["dc.contributor.author","Murina, Olga"],["dc.contributor.author","Leitch, Andrea"],["dc.contributor.author","Higgs, Martin R."],["dc.contributor.author","Bicknell, Louise S."],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Blackford, Andrew N."],["dc.contributor.author","Zlatanou, Anastasia"],["dc.contributor.author","Mackenzie, Karen J."],["dc.contributor.author","Reddy, Kaalak"],["dc.contributor.author","Halachev, Mihail"],["dc.contributor.author","McGlasson, Sarah"],["dc.contributor.author","Reijns, Martin A. M."],["dc.contributor.author","Fluteau, Adeline"],["dc.contributor.author","Martin, Carol-Anne"],["dc.contributor.author","Sabbioneda, Simone"],["dc.contributor.author","Elcioglu, Nursel H."],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Greenhalgh, Lynn"],["dc.contributor.author","Chessa, Luciana"],["dc.contributor.author","Maghnie, Mohamad"],["dc.contributor.author","Salim, Mahmoud"],["dc.contributor.author","Bober, Michael B."],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Jackson, Stephen P."],["dc.contributor.author","Hurles, Matthew E."],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Stewart, Grant S."],["dc.contributor.author","Jackson, Andrew P."],["dc.date.accessioned","2017-09-07T11:54:46Z"],["dc.date.available","2017-09-07T11:54:46Z"],["dc.date.issued","2016"],["dc.description.abstract","DNA lesions encountered by replicative polymerases threaten genome stability and cell cycle progression. Here we report the identification of mutations in TRAIP, encoding an E3 RING ubiquitin ligase, in patients with microcephalic primordial dwarfism. We establish that TRAIP relocalizes to sites of DNA damage, where it is required for optimal phosphorylation of H2AX and RPA2 during S-phase in response to ultraviolet (UV) irradiation, as well as fork progression through UV-induced DNA lesions. TRAIP is necessary for efficient cell cycle progression and mutations in TRAIP therefore limit cellular proliferation, providing a potential mechanism for microcephaly and dwarfism phenotypes. Human genetics thus identifies TRAIP as a component of the DNA damage response to replication-blocking DNA lesions."],["dc.identifier.doi","10.1038/ng.3451"],["dc.identifier.gro","3141758"],["dc.identifier.isi","000367255300011"],["dc.identifier.pmid","26595769"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/746"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.eissn","1546-1718"],["dc.relation.issn","1061-4036"],["dc.title","TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]