The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

• DOI: 10.1038/s41436-018-0330-z
• Publication Date: 2018-10-22T07:05:02Z
• Authors: Pleuntje J. van d...; Sandra Jansen; Samantha A. Vergano; Miho Adachi-Fukuda; Yasemin Alanay; Adila AlKindy; Anwar Baban; Allan Bayat; Stefanie Beck-Wödl; Katherine Berry; Emilia K. Bijlsma; Levinus A. Bok; Alwin F.J. Brouwer; Ineke van der Burgt; Philippe M. Campeau; Natalie Canham; Krystyna Chrzanowska; Yoyo W.Y. Chu; Brain H.Y. Chung; Karin Dahan; Marjan De Rademaeker; Anne Destree; Tracy Dudding-Byth; Rachel Earl; Nursel Elcioglu; Ellen R. Elias; Christina Fagerberg; Alice Gardham; Blanca Gener; Erica H. Gerkes; Ute Grasshoff; Arie van Haeringen; Karin R. Heitink; Johanna C. Herkert; Nicolette S. den ...; Denise Horn; David Hunt; Sarina G. Kant; Mitsuhiro Kato; Hülya Kayserili; Rogier Kersseboom; Esra Kilic; Malgorzata Krajew...; Kylin Lammers; Lone W. Laulund; Damien Lederer; Melissa Lees; Vanesa López-Gonz...; Saskia Maas; Grazia M.S. Mancini; Carlo Marcelis; Francisco Martinez; Isabelle Maystadt; Marianne McGuire; Shane McKee; Sarju Mehta; Kay Metcalfe; Jeff Milunsky; Seiji Mizuno; John B. Moeschler; Christian Netzer; Charlotte W. Ocke...; Barbara Oehl-Jasc...; Nobuhiko Okamoto; Sharon N.M. Olmin...; Carmen Orellana; Laurent Pasquier; Caroline Pottinger; Vera Riehmer; Stephen P. Robertson; Maian Roifman; Caroline Rooryck; Fabienne G. Ropers; Monica Rosello; Claudia A.L. Ruiv...; Mahmut S. Sagiroglu; Suzanne C.E.H. Sa...; Amparo Sanchis Calvo; Pelin O. Simsek-K...; Gabriela Soares; Lucia Solaeche; Fatma Mujgan Sonmez; Miranda Splitt; Duco Steenbeek; Alexander P.A. St...; Constance T.R.M. ...; Saori Tanabe; Eyyup Uctepe; G. Eda Utine; Hermine E. Veenst...; Sunita Venkateswaran; Catheline Vilain; Catherine Vincent...; Anneke T. Vulto-v...; Patricia Wheeler; Golder N. Wilson; Louise C. Wilson; Bernd Wollnik; Tomoki Kosho; Dagmar Wieczorek; Evan Eichler; Rolph Pfundt; Bert B.A. de Vries; Jill Clayton-Smith; Gijs W.E. Santen
• Keywords: Male; bias; Coffin–Siris syndrome; Anomalías Múltiples; Chromosomal Proteins, Non-Histone; Cara; Penetrance; PHENOTYPE; Variación Genética; Preescolar; Factores de Transcripción; Recién Nacido; Exoma; Micrognatismo; Coffin-Siris syndrome; Exome; Masculino; Child; Adolescente; Persona de Mediana Edad; 0303 health sciences; Adulto; Femenino; Proteínas de Unión al ADN; Middle Aged; Humanos; 3. Good health; DNA-Binding Proteins; intellectual disability; Niño; Child, Preschool; Female; Hand Deformities, Congenital; Adult; Adolescent; EMC OR-01; Micrognathism; 610; Cuello; CHROMATIN-REMODELING COMPLEX; Article; 03 medical and health sciences; All institutes and research themes of the Radboud University Medical Center; Intellectual Disability; Proteínas Cromosómicas no Histona; Humans; Abnormalities, Multiple; Genetic Association Studies; Discapacidad Intelectual; Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience; Mutación; MUTATIONS; Infant, Newborn; Deformidades Congénitas de la Mano; Genetic Variation; Infant; Radboudumc 9: Rare cancers RIHS: Radboud Institute for Health Sciences; Lactante; ARID1B; Penetrancia; Face; Mutation; Estudios de Asociación Genética; Neck; Transcription Factors

<h2>ABSTRACT</h2><h3>Purpose</h3> Pathogenic variants in ARID1B are one of the most frequent causes intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data representative for identified through unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic phenotypic differences between ARID1B-ID ARID1B-CSS. In parallel, we investigated effect different methods phenotype reporting. <h3>Methods</h3> Clinicians entered clinical an extensive web-based survey. <h3>Results</h3> 79 ARID1B-CSS 64 were included. CSS-associated dysmorphic features, such thick eyebrows, long eyelashes, alae nasi, and/or broad philtrum, small nails or absent fifth distal phalanx hypertrichosis, observed significantly more often (<i>p</i> < 0.001) patients. No other significant identified. <h3>Conclusion</h3> There only minor ARID1B-related disorders seem consist a spectrum, should be managed similarly. demonstrated that collection without explicit option report absence feature (such Human Phenotype Ontology-based methods) tended underestimate gene-related features.