Wollnik, Bernd

[["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","180"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","American Journal of Medical Genetics"],["dc.bibliographiccitation.lastpage","185"],["dc.bibliographiccitation.volume","155A"],["dc.contributor.author","Kayserili, Hülya"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Guven, Gamze"],["dc.contributor.author","Emiroglu, Melike Ulubil"],["dc.contributor.author","Baserer, Nermin"],["dc.contributor.author","Uyguner, Oya"],["dc.date.accessioned","2017-09-07T11:44:22Z"],["dc.date.available","2017-09-07T11:44:22Z"],["dc.date.issued","2011"],["dc.description.abstract","Recessive mutations in COL11A2 (collagen, type XI, alpha 2), are responsible for otospondylomegaepiphyseal dysplasia (OSMED) and non-syndromic hearing loss while dominant mutations are associated with Stickler type III, isolated cleft palate, Robin sequence, non-ophthalmic Stickler syndrome, early onset osteoarthritis and autosomal dominant hearing loss. We describe here the clinical findings of two Turkish cousins with OSMED carrying a novel homozygous truncating mutation in exon 38 of COL11A2 gene, c.2763delT, identified on cDNA and confirmed at gDNA. This mutation is located on triple helix repeat domain of the collagen alpha-2 (XI) chain, where the majority of the previously identified mutations are located. Real-time RT-PCR experiment provided that mutated transcript does not decay completely. Although our analysis displays the partial survival of the mutant transcript from blood tissue, not from cartilage, we propose that this mechanism may play an important role on the variable expressivity of the heterozygous COL11A2 gene mutations. (C) 2010 Wiley-Liss, Inc."],["dc.identifier.doi","10.1002/ajmg.a.33780"],["dc.identifier.gro","3142790"],["dc.identifier.isi","000285889100028"],["dc.identifier.pmid","21204229"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/232"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley-liss"],["dc.relation.issn","1552-4825"],["dc.title","A Novel Homozygous COL11A2 Deletion Causes a C-Terminal Protein Truncation With Incomplete mRNA Decay in a Turkish Patient"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","5893"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","The Journal of Clinical Endocrinology & Metabolism"],["dc.bibliographiccitation.lastpage","5897"],["dc.bibliographiccitation.volume","88"],["dc.contributor.author","Tukel, T."],["dc.contributor.author","Uyguner, Oya"],["dc.contributor.author","Wei, J. Q."],["dc.contributor.author","Yüksel Apak, Memnune"],["dc.contributor.author","Saka, Nurçin"],["dc.contributor.author","Song, D. X."],["dc.contributor.author","Kayserili, Hülya"],["dc.contributor.author","Baş, Firdevs"],["dc.contributor.author","Günöz, Hülya"],["dc.contributor.author","Wilson, Robert C."],["dc.contributor.author","New, M. I."],["dc.contributor.author","Wollnik, Bernd"],["dc.date.accessioned","2017-09-07T11:44:09Z"],["dc.date.available","2017-09-07T11:44:09Z"],["dc.date.issued","2003"],["dc.description.abstract","21-Hydroxylase deficiency is a recessively inherited disorder resulting from mutations in the CYP21 gene. The CYP21 gene is located along with the CYP21P pseudogene in the human leukocyte antigen major histocompatibility complex region on chromosome 6. Molecular diagnosis is difficult due to the 98% similarity of CYP21 and CYP21P genes and the fact that almost all frequently reported mutations reside on the pseudogene. Allele-specific PCR for the 8 most frequently reported point mutations was performed in 31 Turkish families with at least a single 21-hydroxylase-deficient individual. The allele frequencies of the point mutations were as follows: P30L, 0%; IVS2 (AS, A/C-G,-13), 22.5%; G110Delta8nt, 3.2%; I172N, 11.4%; exon 6 cluster (I236N, V237E, M239K), 3.2%; V281L, 0%; Q318X, 8%; and R356W, 9.6%. Large deletions and gene conversions were detected by Southern blot analysis, and the allele frequencies were 9.6% and 22.5%, respectively. Sequence analysis of the gene, performed on patients with only 1 mutated allele, revealed 2 missense mutations (R339H and P435S). A novel semiquantitative PCR/enzyme digestion-based method for the detection of large scale deletions/conversions of the gene was developed for routine diagnostic purposes, and its accuracy was shown by comparison with the results of Southern blot analysis."],["dc.identifier.doi","10.1210/jc.2003-030813"],["dc.identifier.gro","3144032"],["dc.identifier.isi","000187184400051"],["dc.identifier.pmid","14671187"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1611"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Endocrine Soc"],["dc.relation.issn","0021-972X"],["dc.title","A novel semiquantitative polymerase chain reaction/enzyme digestion-based method for detection of large scale deletions/conversions of the CYP21 gene and mutation screening in Turkish families with 21-hydroxylase deficiency"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","352"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Molecular Genetics and Metabolism"],["dc.bibliographiccitation.lastpage","361"],["dc.bibliographiccitation.volume","110"],["dc.contributor.author","Dimopoulou, Aikaterini"],["dc.contributor.author","Fischer, Björn"],["dc.contributor.author","Gardeitchik, Thatjana"],["dc.contributor.author","Schroeter, Phillipe"],["dc.contributor.author","Kayserili, Hülya"],["dc.contributor.author","Schlack, Claire"],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Brum, Jaime Moritz"],["dc.contributor.author","Barisic, Ingeborg"],["dc.contributor.author","Castori, Marco"],["dc.contributor.author","Spaich, Christiane"],["dc.contributor.author","Fletcher, Elaine"],["dc.contributor.author","Mahayri, Zeina"],["dc.contributor.author","Bhat, Meenakshi"],["dc.contributor.author","Girisha, Katta M."],["dc.contributor.author","Lachlan, Katherine"],["dc.contributor.author","Johnson, Diana"],["dc.contributor.author","Phadke, Shubha"],["dc.contributor.author","Gupta, Neerja"],["dc.contributor.author","Simandlova, Martina"],["dc.contributor.author","Kabra, Madhulika"],["dc.contributor.author","David, Albert"],["dc.contributor.author","Nijtmans, Leo"],["dc.contributor.author","Chitayat, David"],["dc.contributor.author","Tuysuz, Beyhan"],["dc.contributor.author","Brancati, Francesco"],["dc.contributor.author","Mundlos, Stefan"],["dc.contributor.author","Van Maldergem, Lionel"],["dc.contributor.author","Morava, Eva"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Kornak, Uwe"],["dc.date.accessioned","2017-09-07T11:47:04Z"],["dc.date.available","2017-09-07T11:47:04Z"],["dc.date.issued","2013"],["dc.description.abstract","Autosomal recessive cutis laxa type 2B (ARCL2B; OMIM # 612940) is a segmental progeroid disorder caused by mutations in PYCR1 encoding pyrroline-5-carboxylate reductase 1, which is part of the conserved proline de novo synthesis pathway. Here we describe 33 patients with PYCR1-related ARCL from 27 families with initial diagnoses varying between wrinkly skin syndrome, gerodermia osteodysplastica, De Barsy syndrome or more severe progeria syndromes. Given the difficult differential diagnosis of ARCL syndromes we performed a systematic comparison of clinical features of PYCR1-related ARCL. Intrauterine growth retardation, a characteristic triangular facial gestalt, psychomotor retardation, and hypotonia were the most relevant distinctive hallmarks of ARCL due to proline de novo synthesis defects. Corneal clouding or cataracts, athetoid movements, and finger contractures were rather rare features, but had a high predictive value. In our cohort we identified 20 different PYCR1 mutations of which seven were novel. Most of the mutations accumulated in exons 4 to 6. Missense alterations of highly conserved residues were most frequent followed by splice site changes and a single nonsense mutation. Analysis of genotype phenotype correlation revealed that patients with mutations in the first two exons had lower average clinical scores and absent or only mild intellectual disability. Structural analyses predicted interference with PYCR1 multimerization for a subset of missense mutations. These findings have implications for the clinics as well as the pathomechanism of PYCR1-related ARCL. (C) 2013 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.ymgme.2013.08.009"],["dc.identifier.gro","3142262"],["dc.identifier.isi","000326058000025"],["dc.identifier.pmid","24035636"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/6331"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Academic Press Inc Elsevier Science"],["dc.relation.eissn","1096-7206"],["dc.relation.issn","1096-7192"],["dc.title","Genotype phenotype spectrum of PYCR1-related autosomal recessive cutis laxa"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["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","23"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Genetics"],["dc.bibliographiccitation.lastpage","26"],["dc.bibliographiccitation.volume","43"],["dc.contributor.author","Kalay, Ersan"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Aslan, Yakup"],["dc.contributor.author","Brown, Karen E."],["dc.contributor.author","Pohl, Esther"],["dc.contributor.author","Bicknell, Louise S."],["dc.contributor.author","Kayserili, Hülya"],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Tuysuz, Beyhan"],["dc.contributor.author","Nürnberg, Gudrun"],["dc.contributor.author","Kiess, Wieland"],["dc.contributor.author","Koegl, Manfred"],["dc.contributor.author","Baessmann, Ingelore"],["dc.contributor.author","Buruk, Kurtulus"],["dc.contributor.author","Toraman, Bayram"],["dc.contributor.author","Kayipmaz, Saadettin"],["dc.contributor.author","Kul, Sibel"],["dc.contributor.author","Ikbal, Mevlit"],["dc.contributor.author","Turner, Daniel J."],["dc.contributor.author","Taylor, Martin S."],["dc.contributor.author","Aerts, Jan"],["dc.contributor.author","Scott, Carol"],["dc.contributor.author","Milstein, Karen"],["dc.contributor.author","Dollfus, Helene"],["dc.contributor.author","Wieczorek, Dagmar"],["dc.contributor.author","Brunner, Han G."],["dc.contributor.author","Hurles, Matthew"],["dc.contributor.author","Jackson, Andrew P."],["dc.contributor.author","Rauch, Anita"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Karaguzel, Ahmet"],["dc.contributor.author","Wollnik, Bernd"],["dc.date.accessioned","2017-09-07T11:45:06Z"],["dc.date.available","2017-09-07T11:45:06Z"],["dc.date.issued","2011"],["dc.description.abstract","Functional impairment of DNA damage response pathways leads to increased genomic instability. Here we describe the centrosomal protein CEP152 as a new regulator of genomic integrity and cellular response to DNA damage. Using homozygosity mapping and exome sequencing, we identified CEP152 mutations in Seckel syndrome and showed that impaired CEP152 function leads to accumulation of genomic defects resulting from replicative stress through enhanced activation of ATM signaling and increased H2AX phosphorylation."],["dc.identifier.doi","10.1038/ng.725"],["dc.identifier.gro","3142808"],["dc.identifier.isi","000285683500010"],["dc.identifier.pmid","21131973"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/253"],["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","CEP152 is a genome maintenance protein disrupted in Seckel syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","641"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Human Mutation"],["dc.bibliographiccitation.lastpage","648"],["dc.bibliographiccitation.volume","30"],["dc.contributor.author","Chung, Boi-Dinh"],["dc.contributor.author","Kayserili, Hülya"],["dc.contributor.author","Ai, Minrong"],["dc.contributor.author","Freudenberg, Jan"],["dc.contributor.author","Uezmcue, Abdullah"],["dc.contributor.author","Uyguner, Oya"],["dc.contributor.author","Bartels, Cynthia F."],["dc.contributor.author","Hoening, Stefan"],["dc.contributor.author","Ramirez, Alfredo"],["dc.contributor.author","Hanisch, Franz-Georg"],["dc.contributor.author","Nürnberg, Gudrun"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Warman, Matthew L."],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Kubisch, Christian"],["dc.contributor.author","Netzer, Christian"],["dc.date.accessioned","2017-09-07T11:47:31Z"],["dc.date.available","2017-09-07T11:47:31Z"],["dc.date.issued","2009"],["dc.description.abstract","We extend the spectrum of phenotypes caused by mutations in the Wnt/Norrin coreceptor low,density lipoprotein receptor-related protein 5 (LRP5) by identifying two novel types of mutation in related individuals whose presenting features were profound muscle hypotonia, mild mental retardation, blindness, and growth retardation. One mutation removes 6 out of 9 consecutive leucine residues in the LRP5 signal peptide (c.43_60del or p.Leu15_Leu20-del), which impairs polypeptide entry into the endoplasmic reticulum (ER), trafficking to the cell membrane, and signal transduction. The second mutation resulted front nonhomologous recombination between Alu repeat sequences, which deleted exons 14-16 and would produce a nonfunctional, truncated, and frameshifted polypeptide, if expressed [chr11:g. (138714471387511)(1387963613879700) del (NW_925106.1) or p.Pro1010GlnfsX38]. We confirmed that the length of the LRP5 signal peptide poly-leucine repeat is polymorphic in the general population, and, importantly, we were able to demonstrate in independent in vitro assays that different allele sizes affect receptor processing and signal transduction. Consequently, this polymorphism may have physiologic effects in vivo. This latter finding is relevant since through a genomewide search we identified nearly 400 human proteins that contain poly-leucine repeats within their signal peptide. We chose 18 of these proteins and genotyped the underlying trinucleotide repeat in healthy Caucasian individuals. More than one length allele was observed in one-half of the proteins. We therefore propose that natural variation in poly-leucine-stretches within signal peptides constitutes a currently unrecognized source of variability in protein translation and expression. Hum Mutat 30, 641-648, 2009. (C) 2008 Wiley-Liss, Inc."],["dc.identifier.doi","10.1002/humu.20916"],["dc.identifier.gro","3143131"],["dc.identifier.isi","000265006400018"],["dc.identifier.pmid","19177549"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/611"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Deutsche Forschungsgemeinschaft (DFG) [NE 826/3-2]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley-liss"],["dc.relation.issn","1059-7794"],["dc.title","A Mutation in the Signal Sequence of LRP5 in a Family With an Osteoporosis-Pseudoglioma Syndrome (OPPG)-Like Phenotype Indicates a Novel Disease Mechanism for Trinucleotide Repeats"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","76"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Human Mutation"],["dc.bibliographiccitation.lastpage","85"],["dc.bibliographiccitation.volume","35"],["dc.contributor.author","Murray, Jennie E."],["dc.contributor.author","Bicknell, Louise S."],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Duker, Angela L."],["dc.contributor.author","van Kogelenberg, Margriet"],["dc.contributor.author","Haghayegh, Sara"],["dc.contributor.author","Wieczorek, Dagmar"],["dc.contributor.author","Kayserili, Hülya"],["dc.contributor.author","Albert, Michael H."],["dc.contributor.author","Wise, Carol A."],["dc.contributor.author","Brandon, January"],["dc.contributor.author","Kleefstra, Tjitske"],["dc.contributor.author","Warris, Adilia"],["dc.contributor.author","van der Flier, Michiel"],["dc.contributor.author","Bamforth, J. Steven"],["dc.contributor.author","Doonanco, Kurston"],["dc.contributor.author","Ades, Lesley"],["dc.contributor.author","Ma, Alan"],["dc.contributor.author","Field, Michael"],["dc.contributor.author","Johnson, Diana"],["dc.contributor.author","Shackley, Fiona"],["dc.contributor.author","Firth, Helen"],["dc.contributor.author","Woods, C. Geoffrey"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Gatti, Richard A."],["dc.contributor.author","Hurles, Matthew"],["dc.contributor.author","Bober, Michael B."],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Jackson, Andrew P."],["dc.date.accessioned","2017-09-07T11:46:56Z"],["dc.date.available","2017-09-07T11:46:56Z"],["dc.date.issued","2014"],["dc.description.abstract","Ligase IV syndrome is a rare differential diagnosis for Nijmegen breakage syndrome owing to a shared predisposition to lympho-reticular malignancies, significant microcephaly, and radiation hypersensitivity. Only 16 cases with mutations in LIG4 have been described to date with phenotypes varying from malignancy in developmentally normal individuals, to severe combined immunodeficiency and early mortality. Here, we report the identification of biallelic truncating LIG4 mutations in 11 patients with microcephalic primordial dwarfism presenting with restricted prenatal growth and extreme postnatal global growth failure (average OFC -10.1 s.d., height -5.1 s.d.). Subsequently, most patients developed thrombocytopenia and leucopenia later in childhood and many were found to have previously unrecognized immunodeficiency following molecular diagnosis. None have yet developed malignancy, though all patients tested had cellular radiosensitivity. A genotype-phenotype correlation was also noted with position of truncating mutations corresponding to disease severity. This work extends the phenotypic spectrum associated with LIG4 mutations, establishing that extreme growth retardation with microcephaly is a common presentation of bilallelic truncating mutations. Such growth failure is therefore sufficient to consider a diagnosis of LIG4 deficiency and early recognition of such cases is important as bone marrow failure, immunodeficiency, and sometimes malignancy are long term sequelae of this disorder. Published 2013 Wiley Periodicals, Inc."],["dc.identifier.doi","10.1002/humu.22461"],["dc.identifier.gro","3142221"],["dc.identifier.isi","000329678600012"],["dc.identifier.pmid","24123394"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/5876"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley-blackwell"],["dc.relation.eissn","1098-1004"],["dc.relation.issn","1059-7794"],["dc.title","Extreme Growth Failure is a Common Presentation of Ligase IV Deficiency"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3282"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","American Journal of Medical Genetics"],["dc.bibliographiccitation.lastpage","3288"],["dc.bibliographiccitation.volume","170"],["dc.contributor.author","Bögershausen, Nina"],["dc.contributor.author","Altunoglu, Umut"],["dc.contributor.author","Beleggia, Filippo"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Kayserili, Hülya"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Wollnik, Bernd"],["dc.date.accessioned","2017-09-07T11:44:31Z"],["dc.date.available","2017-09-07T11:44:31Z"],["dc.date.issued","2016"],["dc.description.abstract","Kabuki syndrome (KS) is a rare developmental disorder characterized by multiple congenital malformations, postnatal growth retardation, intellectual disability, and recognizable facial features. It is mainly caused by mutations in either KMT2D or KDM6A. We describe a 14-year-old boy with KS presenting with an unusual combination of bilateral microphthalmia with orbital cystic venous lymphatic malformation and neonatal cholestasis with bile duct paucity, in addition to the typical clinical features of KS. We identified the novel KMT2D mutation c.10588delC, p.(Glu3530Serfs 128) by Mendeliome (Illumina TruSight One (R)) sequencing, a next generation sequencing panel targeting 4,813 genes linked to human genetic disease. We analyzed the Mendeliome data for additional mutations which might explain the exceptional clinical presentation of our patient but did not find any, leading us to suspect that the above named symptoms might be part of the KMT2D-associated spectrum of anomalies. We thus extend the range of KS-associated malformations and propose a hypothetical connection between KMT2D and Notch signaling. (C) 2016 Wiley Periodicals, Inc."],["dc.identifier.doi","10.1002/ajmg.a.37931"],["dc.identifier.gro","3141596"],["dc.identifier.isi","000388199100035"],["dc.identifier.pmid","27530281"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: German Federal Ministry of Education and Research (BMBF) [01GM0801]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1552-4833"],["dc.relation.issn","1552-4825"],["dc.title","An Unusual Presentation of Kabuki Syndrome with Orbital Cysts, Microphthalmia, and Cholestasis with Bile Duct Paucity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","639"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","European Journal of Human Genetics"],["dc.bibliographiccitation.lastpage","644"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Yüksel Apak, Memnune"],["dc.contributor.author","Boegershausen, Nina"],["dc.contributor.author","Pawlik, Barbara"],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Apak, Selcuk"],["dc.contributor.author","Uyguner, Oya"],["dc.contributor.author","Milz, Esther"],["dc.contributor.author","Nürnberg, Gudrun"],["dc.contributor.author","Karaman, Birsen"],["dc.contributor.author","Gulgoren, Ayan"],["dc.contributor.author","Grzeschik, Karl-Heinz"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Kayserili, Hülya"],["dc.contributor.author","Wollnik, Bernd"],["dc.date.accessioned","2017-09-07T11:48:52Z"],["dc.date.available","2017-09-07T11:48:52Z"],["dc.date.issued","2012"],["dc.description.abstract","Indian hedgehog (Ihh) signaling is a major determinant of various processes during embryonic development and has a pivotal role in embryonic skeletal development. A specific spatial and temporal expression of Ihh within the developing limb buds is essential for accurate digit outgrowth and correct digit number. Although missense mutations in IHH cause brachydactyly type A1, small tandem duplications involving the IHH locus have recently been described in patients with mild syndactyly and craniosynostosis. In contrast, a similar to 600-kb deletion 5' of IHH in the doublefoot mouse mutant (Dbf) leads to severe polydactyly without craniosynostosis, but with craniofacial dysmorphism. We now present a patient resembling acrocallosal syndrome (ACS) with extensive polysyndactyly of the hands and feet, craniofacial abnormalities including macrocephaly, agenesis of the corpus callosum, dysplastic and low-set ears, severe hypertelorism and profound psychomotor delay. Single-nucleotide polymorphism (SNP) array copy number analysis identified a similar to 900-kb duplication of the IHH locus, which was confirmed by an independent quantitative method. A fetus from a second pregnancy of the mother by a different spouse showed similar craniofacial and limb malformations and the same duplication of the IHH-locus. We defined the exact breakpoints and showed that the duplications are identical tandem duplications in both sibs. No copy number changes were observed in the healthy mother. To our knowledge, this is the first report of a human phenotype similar to the Dbf mutant and strikingly overlapping with ACS that is caused by a copy number variation involving the IHH locus on chromosome 2q35. European Journal of Human Genetics (2012) 20, 639-644; doi:10.1038/ejhg.2011.250; published online 11 January 2012"],["dc.identifier.doi","10.1038/ejhg.2011.250"],["dc.identifier.gro","3142530"],["dc.identifier.isi","000304200000012"],["dc.identifier.pmid","22234151"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8891"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1018-4813"],["dc.title","A large duplication involving the IHH locus mimics acrocallosal syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]