Expanding the clinical spectrum of the 'HDAC8-phenotype' - implications for molecular diagnostics, counseling and risk prediction

Autor: I, Parenti, C, Gervasini, J, Pozojevic, K S, Wendt, E, Watrin, J, Azzollini, D, Braunholz, K, Buiting, A, Cereda, H, Engels, L, Garavelli, R, Glazar, B, Graffmann, L, Larizza, H J, Lüdecke, M, Mariani, M, Masciadri, J, Pié, F J, Ramos, S, Russo, A, Selicorni, M, Stefanova, T M, Strom, R, Werner, J, Wierzba, G, Zampino, G, Gillessen-Kaesbach, D, Wieczorek, F J, Kaiser
Přispěvatelé: Cell biology, Università degli Studi di Milano [Milano] (UNIMI), Institut für Humangenetik Lübeck, Universität zu Lübeck [Lübeck], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione 'Istituto Neurologico Nazionale C. Mondino', Institute of Human Genetics - Institut für Humangenetik [Essen], Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen)-Universitat Duisberg-Essen, IRCCS Istituto Auxologico Italiano, Clinica Pediatrica, Università cattolica del Sacro Cuore [Milano] (Unicatt), Bundesministerium für Bildung und Forschung, ZonMw, Agence Nationale de la Recherche, Society of Pediatric Psychology, FIS PI12-01318, Spain's Ministry of Health-ISCIII, B20, Gobierno de Aragón, SAL31-ID 17292, Accordo Quadro Università-Regione Lombardia, Università degli Studi di Milano = University of Milan (UNIMI), Universität zu Lübeck = University of Lübeck [Lübeck], Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB)
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Clinical Genetics, 89(5), 564-573. Wiley-Blackwell Publishing Ltd
Clinical Genetics
Clinical Genetics, Wiley, 2016, 89 (5), pp.564-573. ⟨10.1111/cge.12717⟩
Clinical Genetics, 2016, 89 (5), pp.564-573. ⟨10.1111/cge.12717⟩
ISSN: 0009-9163
1399-0004
DOI: 10.1111/cge.12717⟩
Popis: International audience; Cornelia de Lange syndrome (CdLS) is a clinically heterogeneous disorder characterized by typical facial dysmorphism, cognitive impairment and multiple congenital anomalies. Approximately 75% of patients carry a variant in one of the five cohesin-related genes NIPBL, SMC1A, SMC3, RAD21 and HDAC8. Herein we report on the clinical and molecular characterization of eleven patients carrying ten distinct variants in HDAC8. Given the high number of variants identified so far, we advise sequencing of HDAC8 as an indispensable part of the routine molecular diagnostic for patients with CdLS or CdLS-overlapping features. The phenotype of our patients is very broad whereas males tend to be more severely affected than females, who instead often present with less canonical CdLS features. The extensive clinical variability observed in the heterozygous females might be at least partially associated with a completely skewed X-inactivation, observed in seven out of eight female patients. Our cohort also includes two affected siblings whose unaffected mother was found to be mosaic for the causative mutation inherited to both affected children. This further supports the urgent need for an integration of highly sensitive sequencing technology to allow an appropriate molecular diagnostic, genetic counselling and risk prediction
Databáze: OpenAIRE
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