Browsing by Author "Simsek-Kiper, Pelin Ozlem"

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    A comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling
    (OXFORD UNIV PRESS, 2013-01-01) Wieczorek, Dagmar; Boegershausen, Nina; Beleggia, Filippo; Steiner-Haldenstaett, Sabine; Pohl, Esther; Li, Yun; Milz, Esther; Martin, Marcel; Thiele, Holger; Altmueller, Janine; Alanay, Yasemin; Kayserili, Hulya; Klein-Hitpass, Ludger; Bohringer, Stefan; Wollstein, Andreas; Albrecht, Beate; Boduroglu, Koray; Caliebe, Almuth; Chrzanowska, Krystyna; Cogulu, Ozgur; Cristofoli, Francesca; Czeschik, Johanna Christina; Devriendt, Koenraad; Dotti, Maria Teresa; Elcioglu, Nursel; Gener, Blanca; Goecke, Timm O.; Krajewska-Walasek, Malgorzata; Guillen-Navarro, Encarnacion; Hayek, Joussef; Houge, Gunnar; Kilic, Esra; Simsek-Kiper, Pelin Ozlem; Lopez-Gonzalez, Vanesa; Kuechler, Alma; Lyonnet, Stanislas; Mari, Francesca; Marozza, Annabella; Dramard, Michele Mathieu; Mikat, Barbara; Morin, Gilles; Morice-Picard, Fanny; Ozkinay, Ferda; Rauch, Anita; Renieri, Alessandra; Tinschert, Sigrid; Utine, G. Eda; Vilain, Catheline; Vivarelli, Rossella; Zweier, Christiane; Nuernberg, Peter; Rahmann, Sven; Vermeesch, Joris; Luedecke, Hermann-Josef; Zeschnigk, Michael; Wollnik, Bernd
    Chromatin remodeling complexes are known to modify chemical marks on histones or to induce conformational changes in the chromatin in order to regulate transcription. Denovodominant mutations in different members of the SWI/SNF chromatin remodeling complex have recently been described in individuals with Coffin-Siris (CSS) and Nicolaides-Baraitser (NCBRS) syndromes. Using a combination of whole-exome sequencing, NGS-based sequencing of 23 SWI/SNF complex genes, and molecular karyotyping in 46 previously undescribed individuals with CSS and NCBRS, we identified a de novo 1-bp deletion (c.677delG, p.Gly226Glufs{*}53) and a de novo missense mutation (c.914G>T, p.Cys305Phe) in PHF6 in two individuals diagnosed with CSS. PHF6 interacts with the nucleosome remodeling and deacetylation ( NuRD) complex implicating dysfunction of a second chromatin remodeling complex in the pathogenesis of CSS-like phenotypes. Altogether, we identified mutations in 60\% of the studied individuals (28/46), located in the genes ARID1A, ARID1B, SMARCB1, SMARCE1, SMARCA2, and PHF6. We show that mutations in ARID1B are the main cause of CSS, accounting for 76\% of identified mutations. ARID1B and SMARCB1 mutations were also found in individuals with the initial diagnosis of NCBRS. These individuals apparently belong to a small subset who display an intermediate CSS/NCBRS phenotype. Our proposed genotype-phenotype correlations are important for molecular screening strategies.
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    Clinical and Radiographic Features of the Autosomal Recessive form of Brachyolmia Caused by PAPSS2 Mutations
    (WILEY, 2013-01-01) Iida, Aritoshi; Simsek-Kiper, Pelin Ozlem; Mizumoto, Shuji; Hoshino, Touma; Elcioglu, Nursel; Horemuzova, Eva; Geiberger, Stefan; Yesil, Gozde; Kayserili, Hulya; Utine, Gulen Eda; Boduroglu, Koray; Watanabe, Shigehiko; Ohashi, Hirofumi; Alanay, Yasemin; Sugahara, Kazuyuki; Nishimura, Gen; Ikegawa, Shiro
    Brachyolmia is a heterogeneous skeletal dysplasia characterized by generalized platyspondyly without significant long-bone abnormalities. Based on the mode of inheritance and radiographic features, at least three types of brachyolmia have been postulated. We recently identified an autosomal recessive form of brachyolmia that is caused by loss-of-function mutations of PAPSS2, the gene encoding PAPS (3-phosphoadenosine 5-phosphosulfate) synthase 2. To understand brachyolmia caused by PAPSS2 mutations (PAPSS2-brachyolmia), we extended our PAPSS2 mutation analysis to 13 patients from 10 families and identified homozygous or compound heterozygous mutations in all. Nine different mutations were found: three splice donor-site mutations, three missense mutations, and three insertion or deletion mutations within coding regions. In vitro enzyme assays showed that the missense mutations were also loss-of-function mutations. Phenotypic characteristics of PAPSS2-brachyolmia include short-trunk short stature, normal intelligence and facies, spinal deformity, and broad proximal interphalangeal joints. Radiographic features include platyspondyly with rectangular vertebral bodies and irregular end plates, broad ilia, metaphyseal changes of the proximal femur, including short femoral neck and striation, and dysplasia of the short tubular bones. PAPSS2-brachyolmia includes phenotypes of the conventional clinical concept of brachyolmia, the Hobaek and Toledo types, and is associated with abnormal androgen metabolism. (C) 2013 Wiley Periodicals, Inc.
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    Expanding the clinical and mutational spectrum of the Ehlers-Danlos syndrome, dermatosparaxis type
    (NATURE PUBLISHING GROUP, 2016-01-01) Van Damme, Tim; Colige, Alain; Syx, Delfien; Giunta, Cecilia; Lindert, Uschi; Rohrbach, Marianne; Aryani, Omid; Alanay, Yasemin; Simsek-Kiper, Pelin Ozlem; Kroes, Hester Y.; Devriendt, Koen; Thiry, Marc; Symoens, Sofie; De Paepe, Anne; Malfait, Fransiska
    Purpose: The Ehlers-Danlos syndrome (EDS), dermatosparaxis type, is a recessively inherited connective tissue disorder caused by deficient activity of ADAMTS-2, an enzyme that cleaves the amino terminal propeptide domain of types I, II, and III procollagen. Only 10 EDS dermatosparaxis patients have been reported, all presenting a recognizable phenotype with characteristic facial gestalt, extreme skin fragility and. laxity, excessive bruising