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27 results on '"Simsek‐Kiper, Pelin Özlem"'

11. A Long-Term Follow-Up of a Patient with a Novel PORCNVariant and Additional Clinical Features

Author

Akalin, Akçahan, Grzeschik, Karl-Heinz, Utine, Eda, Boduroğlu, Koray, and Simsek-Kiper, Pelin Özlem

Abstract

Introduction:Focal dermal hypoplasia (FDH) is a genodermatosis also known as Goltz-Gorlin syndrome caused by pathogenic variants in the PORCNgene and inherited in an X-linked dominant manner. Given the course of X-linked dominant inheritance, affected males can only survive in the state of mosaicism for a PORCNpathogenic variant or in the presence of XXY karyotype. FDH is a multisystemic disorder in which cutaneous, ocular, and skeletal systems are primarily affected. Patients also may display intellectual disability and central nervous system abnormalities, yet most may have normal mental development. Case Presentation:We report on a currently 11-year-old female patient with a novel missense heterozygous PORCNvariant who exhibited classical ectodermal, skeletal, and ocular findings in addition to mild intellectual disability, left-side diaphragm eventration, and puberty precox, a finding yet unreported in the literature. Conclusion:With this report, we aimed to expand the mutational spectrum and give insight into the importance of neurologic and skeletal system evaluation among other clinical features of FDH. Although gastrointestinal and genitourinary problems can occur during the course of the disease, to our knowledge, left-side diaphragm eventration and puberty precox are new features that have not been reported previously.

Published
2024
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13. HEATR3 variants impair nuclear import of uL18 (RPL5) and drive Diamond-Blackfan anemia

Author

O’Donohue, Marie-Françoise, Da Costa, Lydie L.M., Lezzerini, Marco, Unal, Sule, Joret, Clément, Bartels, Marije, Brilstra, Eva, Scheijde-Vermeulen, Marijn, Wacheul, Ludivine, De Keersmaecker, Kim, Vereecke, Stijn, Labarque, Veerle, Saby, Manon, Lefevre, Sophie D., Platon, Jessica, Montel-Lehry, Nathalie, Laugero, Nathalie, Lacazette, Eric, van Gassen, Koen K.L.I., Houtkooper, Riekelt R.H., Simsek-Kiper, Pelin Özlem P.O., Leblanc, Thierry, Yarali, Nese, Cetinkaya, Arda, Akarsu, Nurten Ayse, Gleizes, Pierre-Emmanuel, Lafontaine, Denis, MacInnes, Alyson Winfried, O’Donohue, Marie-Françoise, Da Costa, Lydie L.M., Lezzerini, Marco, Unal, Sule, Joret, Clément, Bartels, Marije, Brilstra, Eva, Scheijde-Vermeulen, Marijn, Wacheul, Ludivine, De Keersmaecker, Kim, Vereecke, Stijn, Labarque, Veerle, Saby, Manon, Lefevre, Sophie D., Platon, Jessica, Montel-Lehry, Nathalie, Laugero, Nathalie, Lacazette, Eric, van Gassen, Koen K.L.I., Houtkooper, Riekelt R.H., Simsek-Kiper, Pelin Özlem P.O., Leblanc, Thierry, Yarali, Nese, Cetinkaya, Arda, Akarsu, Nurten Ayse, Gleizes, Pierre-Emmanuel, Lafontaine, Denis, and MacInnes, Alyson Winfried

Abstract

The congenital bone marrow failure syndrome Diamond-Blackfan anemia (DBA) is typically associated with variants in ribosomal protein (RP) genes impairing erythroid cell development. Here we report multiple individuals with biallelic HEATR3 variants exhibiting bone marrow failure, short stature, facial and acromelic dysmorphic features, and intellectual disability. These variants destabilize a protein whose yeast homolog is known to synchronize the nuclear import of RPs uL5 (RPL11) and uL18 (RPL5), which are both critical for producing ribosomal subunits and for stabilizing the p53 tumor suppressor when ribosome biogenesis is compromised. Expression of HEATR3 variants or repression of HEATR3 expression in primary cells, cell lines of various origins, and yeast models impairs growth, differentiation, pre–ribosomal RNA processing, and ribosomal subunit formation reminiscent of DBA models of large subunit RP gene variants. Consistent with a role of HEATR3 in RP import, HEATR3-depleted cells or patient-derived fibroblasts display reduced nuclear accumulation of uL18. Hematopoietic progenitor cells expressing HEATR3 variants or small-hairpin RNAs knocking down HEATR3 synthesis reveal abnormal acceleration of erythrocyte maturation coupled to severe proliferation defects that are independent of p53 activation. Our study uncovers a new pathophysiological mechanism leading to DBA driven by biallelic HEATR3 variants and the destabilization of a nuclear import protein important for ribosome biogenesis., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2022

15. More than meets the eye: Expanding and reviewing the clinical and mutational spectrum of brittle cornea syndrome

Author

Dhooge, Tibbe, Van Damme, Tim, Syx, Delfien, Mosquera, Laura Muiño, Nampoothiri, Sheela, Radhakrishnan, Anil, Simsek-Kiper, Pelin Özlem P.O., Utine, Gülen Eda, Bonduelle, Maryse, Migeotte, Isabelle, Essawi, Osama, Ceylaner, Serdar, Al Kindy, Adila, Tinkle, Brad, Symoens, Sofie, Malfait, Fransiska, Dhooge, Tibbe, Van Damme, Tim, Syx, Delfien, Mosquera, Laura Muiño, Nampoothiri, Sheela, Radhakrishnan, Anil, Simsek-Kiper, Pelin Özlem P.O., Utine, Gülen Eda, Bonduelle, Maryse, Migeotte, Isabelle, Essawi, Osama, Ceylaner, Serdar, Al Kindy, Adila, Tinkle, Brad, Symoens, Sofie, and Malfait, Fransiska

Abstract

Brittle cornea syndrome (BCS) is a rare autosomal recessive disorder characterized by corneal thinning and fragility, leading to corneal rupture, the main hallmark of this disorder. Non-ocular symptoms include not only hearing loss but also signs of connective tissue fragility, placing it in the Ehlers-Danlos syndrome (EDS) spectrum. It is caused by biallelic pathogenic variants in ZNF469 or PRDM5, which presumably encode transcription factors for extracellular matrix components. We report the clinical and molecular features of nine novel BCS families, four of which harbor variants in ZNF469 and five in PRDM5. We also performed a genotype- and phenotype-oriented literature overview of all (n = 85) reported patients with ZNF469 (n = 53) and PRDM5 (n = 32) variants. Musculoskeletal findings may be the main reason for referral and often raise suspicion of another heritable connective tissue disorder, such as kyphoscoliotic EDS, osteogenesis imperfecta, or Marfan syndrome, especially when a corneal rupture has not yet occurred. Our findings highlight the multisystemic nature of BCS and validate its inclusion in the EDS classification. Importantly, gene panels for heritable connective tissue disorders should include ZNF469 and PRDM5 to allow for timely diagnosis and appropriate preventive measures for this rare condition., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2021

16. A mutation screen in patients with Kabuki syndrome

Author

Li, Yun, Bögershausen, Nina, Alanay, Yasemin, Simsek Kiper, Pelin Özlem, Plume, Nadine, Keupp, Katharina, Pohl, Esther, Pawlik, Barbara, Rachwalski, Martin, Milz, Esther, Thoenes, Michaela, Albrecht, Beate, Prott, Eva-Christina, Lehmkühler, Margret, Demuth, Stephanie, Utine, Gülen Eda, Boduroglu, Koray, Frankenbusch, Katja, Borck, Guntram, Gillessen-Kaesbach, Gabriele, Yigit, Gökhan, Wieczorek, Dagmar, and Wollnik, Bernd

Published
2011
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17. Further expanding the mutational spectrum of brain abnormalities, neurodegeneration, and dysosteosclerosis: A rare disorder with neurologic regression and skeletal features

Author

Kındış, Erdem, primary, Simsek‐Kiper, Pelin Özlem, additional, Koşukcu, Can, additional, Taşkıran, Ekim Z., additional, Göçmen, Rahşan, additional, Utine, Eda, additional, Haliloğlu, Göknur, additional, Boduroğlu, Koray, additional, and Alikaşifoğlu, Mehmet, additional

Published
2021
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18. A comprehensive molecular study on Coffin–Siris and Nicolaides–Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling

Author

Wieczorek, Dagmar, Bögershausen, Nina, Beleggia, Filippo, Steiner-Haldenstätt, Sabine, Pohl, Esther, Li, Yun, Milz, Esther, Martin, Marcel, Thiele, Holger, Altmüller, Janine, Alanay, Yasemin, Kayserili, Hülya, Klein-Hitpass, Ludger, Böhringer, 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, Małgorzata, Guillén-Navarro, Encarnación, Hayek, Joussef, Houge, Gunnar, Kilic, Esra, Simsek-Kiper, Pelin Özlem, López-González, Vanesa, Kuechler, Alma, Lyonnet, Stanislas, Mari, Francesca, Marozza, Annabella, Mathieu Dramard, Michèle, Mikat, Barbara, Morin, Gilles, Morice-Picard, Fanny, Özkinay, Ferda, Rauch, Anita, Renieri, Alessandra, Tinschert, Sigrid, Utine, G. Eda, Vilain, Catheline, Vivarelli, Rossella, Zweier, Christiane, Nürnberg, Peter, Rahmann, Sven, Vermeesch, Joris, Lüdecke, Hermann-Josef, Zeschnigk, Michael, and Wollnik, Bernd

Published
2013
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21. A comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling

Author

Wieczorek, Dagmar, Bögershausen, Nina, Beleggia, Filippo, Steiner-Haldenstätt, Sabine, Pohl, Esther, Li, Yun, Milz, Esther, Martin, Marcel, Thiele, Holger, Altmüller, Janine, Alanay, Yasemin, Kayserili, Hülya, Klein-Hitpass, Ludger, Böhringer, 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, Małgorzata, Guillén-Navarro, Encarnación, Hayek, Joussef, Houge, Gunnar, Kilic, Esra, Simsek-Kiper, Pelin Özlem, López-González, Vanesa, Kuechler, Alma, Lyonnet, Stanislas, Mari, Francesca, Marozza, Annabella, Mathieu Dramard, Michèle, Mikat, Barbara, Morin, Gilles, Morice-Picard, Fanny, Özkinay, Ferda, Rauch, Anita, Renieri, Alessandra, Tinschert, Sigrid, Utine, G. Eda, Vilain, Catheline, Vivarelli, Rossella, Zweier, Christiane, Nürnberg, Peter, Rahmann, Sven, Vermeesch, Joris, Lüdecke, Hermann-Josef, Zeschnigk, Michael, Wollnik, Bernd, Wieczorek, Dagmar, Bögershausen, Nina, Beleggia, Filippo, Steiner-Haldenstätt, Sabine, Pohl, Esther, Li, Yun, Milz, Esther, Martin, Marcel, Thiele, Holger, Altmüller, Janine, Alanay, Yasemin, Kayserili, Hülya, Klein-Hitpass, Ludger, Böhringer, 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, Małgorzata, Guillén-Navarro, Encarnación, Hayek, Joussef, Houge, Gunnar, Kilic, Esra, Simsek-Kiper, Pelin Özlem, López-González, Vanesa, Kuechler, Alma, Lyonnet, Stanislas, Mari, Francesca, Marozza, Annabella, Mathieu Dramard, Michèle, Mikat, Barbara, Morin, Gilles, Morice-Picard, Fanny, Özkinay, Ferda, Rauch, Anita, Renieri, Alessandra, Tinschert, Sigrid, Utine, G. Eda, Vilain, Catheline, Vivarelli, Rossella, Zweier, Christiane, Nürnberg, Peter, Rahmann, Sven, Vermeesch, Joris, Lüdecke, Hermann-Josef, Zeschnigk, Michael, and Wollnik, Bernd

Abstract

Chromatin remodeling complexes are known to modify chemical marks on histones or to induce conformational changes in the chromatin in order to regulate transcription. De novo dominant 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

Published
2017

22. Expanding the clinical and mutational spectrum of the Ehlers-Danlos syndrome, dermatosparaxis type

Author

Van Damme, Tim, Colige, Alain, Syx, Delfien, Giunta, Cecilia, Lindert, Uschi, Rohrbach, Marianne, Aryani, Omid, Alanay, Yasemin, Simsek-Kiper, Pelin Özlem, Kroes, Hester Y, Devriendt, Koen, Thiry, Marc, Symoens, Sofie, De Paepe, Anne, Malfait, Fransiska, Van Damme, Tim, Colige, Alain, Syx, Delfien, Giunta, Cecilia, Lindert, Uschi, Rohrbach, Marianne, Aryani, Omid, Alanay, Yasemin, Simsek-Kiper, Pelin Özlem, Kroes, Hester Y, Devriendt, Koen, Thiry, Marc, Symoens, Sofie, De Paepe, Anne, and Malfait, Fransiska

Published
2016

23. Expanding the clinical and mutational spectrum of the Ehlers-Danlos syndrome, dermatosparaxis type

Author

Genetica Klinische Genetica, Child Health, Van Damme, Tim, Colige, Alain, Syx, Delfien, Giunta, Cecilia, Lindert, Uschi, Rohrbach, Marianne, Aryani, Omid, Alanay, Yasemin, Simsek-Kiper, Pelin Özlem, Kroes, Hester Y, Devriendt, Koen, Thiry, Marc, Symoens, Sofie, De Paepe, Anne, Malfait, Fransiska, Genetica Klinische Genetica, Child Health, Van Damme, Tim, Colige, Alain, Syx, Delfien, Giunta, Cecilia, Lindert, Uschi, Rohrbach, Marianne, Aryani, Omid, Alanay, Yasemin, Simsek-Kiper, Pelin Özlem, Kroes, Hester Y, Devriendt, Koen, Thiry, Marc, Symoens, Sofie, De Paepe, Anne, and Malfait, Fransiska

Published
2016

24. Expanding the clinical and mutational spectrum of the Ehlers–Danlos syndrome, dermatosparaxis type

Author

Van Damme, Tim, primary, Colige, Alain, additional, Syx, Delfien, additional, Giunta, Cecilia, additional, Lindert, Uschi, additional, Rohrbach, Marianne, additional, Aryani, Omid, additional, Alanay, Yasemin, additional, Simsek-Kiper, Pelin Özlem, additional, Kroes, Hester Y., additional, Devriendt, Koen, additional, Thiry, Marc, additional, Symoens, Sofie, additional, De Paepe, Anne, additional, and Malfait, Fransiska, additional

Published
2016
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25. Mutation Update for Kabuki Syndrome GenesKMT2DandKDM6Aand Further Delineation of X-Linked Kabuki Syndrome Subtype 2

Author

Bögershausen, Nina, primary, Gatinois, Vincent, additional, Riehmer, Vera, additional, Kayserili, Hülya, additional, Becker, Jutta, additional, Thoenes, Michaela, additional, Simsek-Kiper, Pelin Özlem, additional, Barat-Houari, Mouna, additional, Elcioglu, Nursel H., additional, Wieczorek, Dagmar, additional, Tinschert, Sigrid, additional, Sarrabay, Guillaume, additional, Strom, Tim M., additional, Fabre, Aurélie, additional, Baynam, Gareth, additional, Sanchez, Elodie, additional, Nürnberg, Gudrun, additional, Altunoglu, Umut, additional, Capri, Yline, additional, Isidor, Bertrand, additional, Lacombe, Didier, additional, Corsini, Carole, additional, Cormier-Daire, Valérie, additional, Sanlaville, Damien, additional, Giuliano, Fabienne, additional, Le Quan Sang, Kim-Hanh, additional, Kayirangwa, Honorine, additional, Nürnberg, Peter, additional, Meitinger, Thomas, additional, Boduroglu, Koray, additional, Zoll, Barbara, additional, Lyonnet, Stanislas, additional, Tzschach, Andreas, additional, Verloes, Alain, additional, Di Donato, Nataliya, additional, Touitou, Isabelle, additional, Netzer, Christian, additional, Li, Yun, additional, Geneviève, David, additional, Yigit, Gökhan, additional, and Wollnik, Bernd, additional

Published
2016
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26. Mutation Update for Kabuki Syndrome Genes KMT2D and KDM6A and Further Delineation of X-Linked Kabuki Syndrome Subtype 2.

Author

Bögershausen, Nina, Gatinois, Vincent, Riehmer, Vera, Kayserili, Hülya, Becker, Jutta, Thoenes, Michaela, Simsek‐Kiper, Pelin Özlem, Barat‐Houari, Mouna, Elcioglu, Nursel H., Wieczorek, Dagmar, Tinschert, Sigrid, Sarrabay, Guillaume, Strom, Tim M., Fabre, Aurélie, Baynam, Gareth, Sanchez, Elodie, Nürnberg, Gudrun, Altunoglu, Umut, Capri, Yline, and Isidor, Bertrand

Abstract

Kabuki syndrome (KS) is a rare but recognizable condition that consists of a characteristic face, short stature, various organ malformations, and a variable degree of intellectual disability. Mutations in KMT2D have been identified as the main cause for KS, whereas mutations in KDM6A are a much less frequent cause.Here, we report a mutation screening in a case series of 347 unpublished patients, in which we identified 12 novel KDM6A mutations (KS type 2) and 208 mutations in KMT2D (KS type 1), 132 of them novel. Two of the KDM6A mutations were maternally inherited and nine were shown to be de novo. We give an up-to-date overview of all published mutations for the two KS genes and point out possible mutation hot spots and strategies for molecular genetic testing. We also report the clinical details for 11 patients with KS type 2, summarize the published clinical information, specifically with a focus on the less well-defined X-linked KS type 2, and comment on phenotype--genotype correlations as well as sex-specific phenotypic differences. Finally, we also discuss a possible role of KDM6A in Kabuki-like Turner syndrome and report a mutation screening of KDM6C (UTY) in male KS patients. [ABSTRACT FROM AUTHOR]

Published
2016
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27. A comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling

Author

Wieczorek, Dagmar, Bögershausen, Nina, Beleggia, Filippo, Steiner-Haldenstätt, Sabine, Pohl, Esther, Li, Yun, Milz, Esther, Martin, Marcel, Thiele, Holger, Altmüller, Janine, Alanay, Yasemin, Kayserili, Hülya, Klein-Hitpass, Ludger, Böhringer, 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, Małgorzata, Guillén-Navarro, Encarnación, Hayek, Joussef, Houge, Gunnar, Kilic, Esra, Simsek-Kiper, Pelin Özlem, López-González, Vanesa, Kuechler, Alma, Lyonnet, Stanislas, Mari, Francesca, Marozza, Annabella, Mathieu Dramard, Michèle, Mikat, Barbara, Morin, Gilles, Morice-Picard, Fanny, Özkinay, Ferda, Rauch, Anita, Renieri, Alessandra, Tinschert, Sigrid, Utine, G. Eda, Vilain, Catheline, Vivarelli, Rossella, Zweier, Christiane, Nürnberg, Peter, Rahmann, Sven, Vermeesch, Joris, Lüdecke, Hermann-Josef, Zeschnigk, Michael, Wollnik, Bernd, Wieczorek, Dagmar, Bögershausen, Nina, Beleggia, Filippo, Steiner-Haldenstätt, Sabine, Pohl, Esther, Li, Yun, Milz, Esther, Martin, Marcel, Thiele, Holger, Altmüller, Janine, Alanay, Yasemin, Kayserili, Hülya, Klein-Hitpass, Ludger, Böhringer, 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, Małgorzata, Guillén-Navarro, Encarnación, Hayek, Joussef, Houge, Gunnar, Kilic, Esra, Simsek-Kiper, Pelin Özlem, López-González, Vanesa, Kuechler, Alma, Lyonnet, Stanislas, Mari, Francesca, Marozza, Annabella, Mathieu Dramard, Michèle, Mikat, Barbara, Morin, Gilles, Morice-Picard, Fanny, Özkinay, Ferda, Rauch, Anita, Renieri, Alessandra, Tinschert, Sigrid, Utine, G. Eda, Vilain, Catheline, Vivarelli, Rossella, Zweier, Christiane, Nürnberg, Peter, Rahmann, Sven, Vermeesch, Joris, Lüdecke, Hermann-Josef, Zeschnigk, Michael, and Wollnik, Bernd

Abstract

Chromatin remodeling complexes are known to modify chemical marks on histones or to induce conformational changes in the chromatin in order to regulate transcription. De novo dominant 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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