Exome sequencing unravels unexpected differential diagnoses in individuals with the tentative diagnosis of Coffin-Siris and Nicolaides-Baraitser syndromes

Bramswig NC, Luedecke HJ, Alanay Y, Albrecht B, Barthelmie A, Boduroglu K, Braunholz D, Caliebe A, Chrzanowska KH, Czeschik JC, Endele S, Graf E, Guillen-Navarro E, Kiper POS, Lopez-Gonzalez V, Parenti I, Pozojevic J, Utine GE, Wieland T, Kaiser FJ, Wollnik B, Strom TM, Wieczorek D (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Human genetics Springer Verlag (Germany)

Book Volume: 134

Pages Range: 553-68

Journal Issue: 6

DOI: 10.1007/s00439-015-1535-8

Abstract

Coffin-Siris syndrome (CSS) and Nicolaides-Baraitser syndrome (NCBRS) are rare intellectual disability/congenital malformation syndromes that represent distinct entities but show considerable clinical overlap. They are caused by mutations in genes encoding members of the BRG1- and BRM-associated factor (BAF) complex. However, there are a number of patients with the clinical diagnosis of CSS or NCBRS in whom the causative mutation has not been identified. In this study, we performed trio-based whole-exome sequencing (WES) in ten previously described but unsolved individuals with the tentative diagnosis of CSS or NCBRS and found causative mutations in nine out of ten individuals. Interestingly, our WES analysis disclosed overlapping differential diagnoses including Wiedemann-Steiner, Kabuki, and Adams-Oliver syndromes. In addition, most likely causative de novo mutations were identified in GRIN2A and SHANK3. Moreover, trio-based WES detected SMARCA2 and SMARCA4 deletions, which had not been annotated in a previous Haloplex target enrichment and next-generation sequencing of known CSS/NCBRS genes emphasizing the advantages of WES as a diagnostic tool. In summary, we discuss the phenotypic and diagnostic challenges in clinical genetics, establish important differential diagnoses, and emphasize the cardinal features and the broad clinical spectrum of BAF complex disorders and other disorders caused by mutations in epigenetic landscapers.

Authors with CRIS profile

Sabine Endele Institute of Human Genetics

Involved external institutions

Universität Duisburg-Essen (UDE) DE Germany (DE) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE) Universität zu Köln DE Germany (DE) Universität zu Lübeck DE Germany (DE) Hacettepe University TR Turkey (TR) Hospital Clínico Universitario Virgen de la Arrixaca ES Spain (ES) Children's Memorial Health Institute / Instytut "Pomnik - Centrum Zdrowia Dziecka" PL Poland (PL) Christian-Albrechts-Universität zu Kiel DE Germany (DE) Kantonsspital Baden CH Switzerland (CH) Acıbadem Üniversitesi TR Turkey (TR)

How to cite

APA:

Bramswig, N.C., Luedecke, H.-J., Alanay, Y., Albrecht, B., Barthelmie, A., Boduroglu, K.,... Wieczorek, D. (2015). Exome sequencing unravels unexpected differential diagnoses in individuals with the tentative diagnosis of Coffin-Siris and Nicolaides-Baraitser syndromes. Human genetics, 134(6), 553-68. https://dx.doi.org/10.1007/s00439-015-1535-8

MLA:

Bramswig, Nuria C., et al. "Exome sequencing unravels unexpected differential diagnoses in individuals with the tentative diagnosis of Coffin-Siris and Nicolaides-Baraitser syndromes." Human genetics 134.6 (2015): 553-68.

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