caa a22 4500 445860723 CHVBK 20180317145442.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s00439-011-1004-y doi (NATIONALLICENCE)springer-10.1007/s00439-011-1004-y A mutation screen in patients with Kabuki syndrome [Elektronische Daten] [Yun Li, Nina Bögershausen, Yasemin Alanay, Pelin Simsek Kiper, Nadine Plume, Katharina Keupp, Esther Pohl, Barbara Pawlik, Martin Rachwalski, Esther Milz, Michaela Thoenes, Beate Albrecht, Eva-Christina Prott, Margret Lehmkühler, Stephanie Demuth, Gülen Utine, Koray Boduroglu, Katja Frankenbusch, Guntram Borck, Gabriele Gillessen-Kaesbach, Gökhan Yigit, Dagmar Wieczorek, Bernd Wollnik] Kabuki syndrome (KS) is one of the classical, clinically well-known multiple anomalies/mental retardation syndromes, mainly characterized by a very distinctive facial appearance in combination with additional clinical signs such as developmental delay, short stature, persistent fingerpads, and urogenital tract anomalies. In our study, we sequenced all 54 coding exons of the recently identified MLL2 gene in 34 patients with Kabuki syndrome. We identified 18 distinct mutations in 19 patients, 11 of 12 tested de novo. Mutations were located all over the gene and included three nonsense mutations, two splice-site mutations, six small deletions or insertions, and seven missense mutations. We compared frequencies of clinical symptoms in MLL2 mutation carriers versus non-carriers. MLL2 mutation carriers significantly more often presented with short stature and renal anomalies (p=0.026 and 0.031, respectively), and in addition, MLL2 carriers obviously showed more frequently a typical facial gestalt (17/19) compared with non-carriers (9/15), although this result was not statistically significant (p=0.1). Mutation-negative patients were subsequently tested for mutations in ten functional candidate genes (e.g. MLL, ASC2, ASH2L, and WDR5), but no convincing causative mutations could be found. Our results indicate that MLL2 is the major gene for Kabuki syndrome with a wide spectrum of de novo mutations and strongly suggest further genetic heterogeneity. Springer-Verlag, 2011 Li Yun Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University Medical Faculty, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany aut Bögershausen Nina Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University Medical Faculty, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany aut Alanay Yasemin Pediatric Genetics Unit, Department of Pediatrics, Hacettepe University Medical Faculty, Ankara, Turkey aut Simsek Kiper Pelin Pediatric Genetics Unit, Department of Pediatrics, Hacettepe University Medical Faculty, Ankara, Turkey aut Plume Nadine Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University Medical Faculty, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany aut Keupp Katharina Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University Medical Faculty, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany aut Pohl Esther Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University Medical Faculty, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany aut Pawlik Barbara Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University Medical Faculty, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany aut Rachwalski Martin Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University Medical Faculty, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany aut Milz Esther Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University Medical Faculty, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany aut Thoenes Michaela Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University Medical Faculty, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany aut Albrecht Beate Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany aut Prott Eva-Christina Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany aut Lehmkühler Margret Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany aut Demuth Stephanie Praxis für Humangenetik, Erfurt, Germany aut Utine Gülen Pediatric Genetics Unit, Department of Pediatrics, Hacettepe University Medical Faculty, Ankara, Turkey aut Boduroglu Koray Pediatric Genetics Unit, Department of Pediatrics, Hacettepe University Medical Faculty, Ankara, Turkey aut Frankenbusch Katja Department of Pediatrics, University of Cologne, Cologne, Germany aut Borck Guntram Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University Medical Faculty, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany aut Gillessen-Kaesbach Gabriele Institut für Humangenetik, Universität zu Lübeck, Lübeck, Germany aut Yigit Gökhan Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University Medical Faculty, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany aut Wieczorek Dagmar Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany aut Wollnik Bernd Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University Medical Faculty, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany aut Human Genetics Springer-Verlag 130/6(2011-12-01), 715-724 0340-6717 130:6<715 2011 130 439 https://doi.org/10.1007/s00439-011-1004-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-011-1004-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Li Yun Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University Medical Faculty, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany aut NATIONALLICENCE 700 1- Bögershausen Nina Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University Medical Faculty, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany aut NATIONALLICENCE 700 1- Alanay Yasemin Pediatric Genetics Unit, Department of Pediatrics, Hacettepe University Medical Faculty, Ankara, Turkey aut NATIONALLICENCE 700 1- Simsek Kiper Pelin Pediatric Genetics Unit, Department of Pediatrics, Hacettepe University Medical Faculty, Ankara, Turkey aut NATIONALLICENCE 700 1- Plume Nadine Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University Medical Faculty, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany aut NATIONALLICENCE 700 1- Keupp Katharina Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University Medical Faculty, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany aut NATIONALLICENCE 700 1- Pohl Esther Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University Medical Faculty, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany aut NATIONALLICENCE 700 1- Pawlik Barbara Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University Medical Faculty, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany aut NATIONALLICENCE 700 1- Rachwalski Martin Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University Medical Faculty, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany aut NATIONALLICENCE 700 1- Milz Esther Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University Medical Faculty, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany aut NATIONALLICENCE 700 1- Thoenes Michaela Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University Medical Faculty, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany aut NATIONALLICENCE 700 1- Albrecht Beate Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany aut NATIONALLICENCE 700 1- Prott Eva-Christina Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany aut NATIONALLICENCE 700 1- Lehmkühler Margret Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany aut NATIONALLICENCE 700 1- Demuth Stephanie Praxis für Humangenetik, Erfurt, Germany aut NATIONALLICENCE 700 1- Utine Gülen Pediatric Genetics Unit, Department of Pediatrics, Hacettepe University Medical Faculty, Ankara, Turkey aut NATIONALLICENCE 700 1- Boduroglu Koray Pediatric Genetics Unit, Department of Pediatrics, Hacettepe University Medical Faculty, Ankara, Turkey aut NATIONALLICENCE 700 1- Frankenbusch Katja Department of Pediatrics, University of Cologne, Cologne, Germany aut NATIONALLICENCE 700 1- Borck Guntram Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University Medical Faculty, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany aut NATIONALLICENCE 700 1- Gillessen-Kaesbach Gabriele Institut für Humangenetik, Universität zu Lübeck, Lübeck, Germany aut NATIONALLICENCE 700 1- Yigit Gökhan Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University Medical Faculty, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany aut NATIONALLICENCE 700 1- Wieczorek Dagmar Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany aut NATIONALLICENCE 700 1- Wollnik Bernd Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University Medical Faculty, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 130/6(2011-12-01), 715-724 0340-6717 130:6<715 2011 130 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer