Phenotype and genotype in Nicolaides-Baraitser syndrome

The Nicolaides-Baraitser Syndrome International Consortium, Sérgio B. Sousa, Raoul C. Hennekam, Omar Abdul-Rahman, Marielle Alders, Silvia Azzarello-Burri, Armand Bottani, Sarah Bowdin, Marco Castori, Valerie Cormier-Daire, Matthew Deardorff, Miquel Del Campo Casanelles, Koenraad Devriendt, Christine Fauth, Isabel Filges, Alan Fryer, Livia Garavelli, Gabriele Gillessen-Kaesback, Bryan Hall, Ohasi Hirofumi & 31 others Susan Holder, Juliane Hoyer, Lucy Jenkins, Jacub Klapeki, Malgorzata Krajewska-Walasek, Tomoki Kosho, Alma Kuechler, Kay MacDermot, Alex Magee, Francesca Mari, Michele Mathieu-Dramard, Melanie Napier, Luis Perez-Jurado, Fanny Morice Picard, Gilles Morin, Victoria Murday, Jacek Pilch, Anne Ronan, Elizabeth Rosser, Gijs W.E. Santen, Richard Scott, Angelo Selicorni, Nora Shannon, Fernando Santos-Simarro, Helen Stewart, Marie Jose van den Boogaard, Catheline Vilain, Joris Vermeesch, Annick Vogels, Emma Wakeling, Dagmar Wieczorek

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Nicolaides-Baraitser syndrome (NCBRS) is an intellectual disability (ID)/multiple congenital anomalies syndrome caused by non-truncating mutations in the ATPase region of SMARCA2, which codes for one of the two alternative catalytic subunits of the BAF chromatin remodeling complex. We analyzed 61 molecularly confirmed cases, including all previously reported patients (n = 47) and 14 additional unpublished individuals. NCBRS is clinically and genetically homogeneous. The cardinal features (ID, short stature, microcephaly, typical face, sparse hair, brachydactyly, prominent interphalangeal joints, behavioral problems and seizures), are almost universally present. There is variability however, as ID can range from severe to mild, and sparse hair may be present only in certain age groups. There may be a correlation between the severity of the ID and presence of seizures, absent speech, short stature and microcephaly. SMARCA2 mutations causing NCBRS are likely to act through a dominant-negative effect. There may be some genotype-phenotype correlations (mutations at domain VI with severe ID and seizures; mutations affecting residues Pro883, Leu946, and Ala1201 with mild phenotypes) but numbers are still too small to draw definitive conclusions.

LanguageEnglish
Pages302-314
Number of pages13
JournalAmerican Journal of Medical Genetics, Part C: Seminars in Medical Genetics
Volume166
Issue number3
DOIs
Publication statusPublished - 1 Jan 2014
Externally publishedYes

Keywords

  • BAF (SWI/SNF) complex
  • Genotype
  • Intellectual disability
  • Natural history
  • Nicolaides-baraitser syndrome
  • Phenotype
  • SMARCA2

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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