TY - JOUR
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 - Pérez-Jurado, Luis A.
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
N1 - Publisher Copyright:
© 2014 Wiley Periodicals, Inc.
PY - 2014/9
Y1 - 2014/9
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 We analyzed 61 molecularly confirmed cases, including all previously reported patients (n = 47) and 14 additional unpublished individuals.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
C2 - 25169058
AN - SCOPUS:84908617685
SN - 1552-4868
VL - 166
SP - 302
EP - 314
JO - American Journal of Medical Genetics, Part C: Seminars in Medical Genetics
JF - American Journal of Medical Genetics, Part C: Seminars in Medical Genetics
IS - 3
ER -