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

29 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 We analyzed 61 molecularly confirmed cases, including all previously reported patients (n = 47) and 14 additional unpublished individuals.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)

Cite this

The Nicolaides-Baraitser Syndrome International Consortium. / Phenotype and genotype in Nicolaides-Baraitser syndrome. In: American Journal of Medical Genetics, Part C: Seminars in Medical Genetics. 2014 ; Vol. 166, No. 3. pp. 302-314.
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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.",
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Phenotype and genotype in Nicolaides-Baraitser syndrome. / The Nicolaides-Baraitser Syndrome International Consortium.

In: American Journal of Medical Genetics, Part C: Seminars in Medical Genetics, Vol. 166, No. 3, 01.01.2014, p. 302-314.

Research output: Contribution to journalArticle

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T1 - Phenotype and genotype in Nicolaides-Baraitser syndrome

AU - The Nicolaides-Baraitser Syndrome International Consortium

AU - Sousa, Sérgio B.

AU - Hennekam, Raoul C.

AU - Abdul-Rahman, Omar

AU - Alders, Marielle

AU - Azzarello-Burri, Silvia

AU - Bottani, Armand

AU - Bowdin, Sarah

AU - Castori, Marco

AU - Cormier-Daire, Valerie

AU - Deardorff, Matthew

AU - Del Campo Casanelles, Miquel

AU - Devriendt, Koenraad

AU - Fauth, Christine

AU - Filges, Isabel

AU - Fryer, Alan

AU - Garavelli, Livia

AU - Gillessen-Kaesback, Gabriele

AU - Hall, Bryan

AU - Hirofumi, Ohasi

AU - Holder, Susan

AU - Hoyer, Juliane

AU - Jenkins, Lucy

AU - Klapeki, Jacub

AU - Krajewska-Walasek, Malgorzata

AU - Kosho, Tomoki

AU - Kuechler, Alma

AU - MacDermot, Kay

AU - Magee, Alex

AU - Mari, Francesca

AU - Mathieu-Dramard, Michele

AU - Napier, Melanie

AU - Perez-Jurado, Luis

AU - Picard, Fanny Morice

AU - Morin, Gilles

AU - Murday, Victoria

AU - Pilch, Jacek

AU - Ronan, Anne

AU - Rosser, Elizabeth

AU - Santen, Gijs W.E.

AU - Scott, Richard

AU - Selicorni, Angelo

AU - Shannon, Nora

AU - Santos-Simarro, Fernando

AU - Stewart, Helen

AU - van den Boogaard, Marie Jose

AU - Vilain, Catheline

AU - Vermeesch, Joris

AU - Vogels, Annick

AU - Wakeling, Emma

AU - Wieczorek, Dagmar

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

KW - BAF (SWI/SNF) complex

KW - Genotype

KW - Intellectual disability

KW - Natural history

KW - Nicolaides-baraitser syndrome

KW - Phenotype

KW - SMARCA2

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U2 - 10.1002/ajmg.c.31409

DO - 10.1002/ajmg.c.31409

M3 - Article

VL - 166

SP - 302

EP - 314

JO - American Journal of Medical Genetics, Part C: Seminars in Medical Genetics

T2 - American Journal of Medical Genetics, Part C: Seminars in Medical Genetics

JF - American Journal of Medical Genetics, Part C: Seminars in Medical Genetics

SN - 1552-4868

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ER -