Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome

Houdt, J. K. J. Van; Nowakowska, Beata; Sousa, Sérgio B.; Schaik, Barbera D.C. van; Seuntjens, Eve; Avonce, Nelson; Sifrim, Alejandro; Abdul‐Rahman, Omar; Boogaard, Marie José H. Van Den; Bottani, Armand; Castori, Marco; Cormier‐Daire, Valérie; Deardorff, Matthew A.; Filges, Isabel; Fryer, Alan; Fryns, J. P.; Gana, Simone; Garavelli, Livia; Gillessen‐Kaesbach, Gabriele; Hall, Bryan D.; Horn, Denise; Huylebroeck, Danny; Klapecki, Jakub; Krajewska‐Walasek, M; Kuechler, Alma; Lines, Matthew A.; Maas, Saskia M.; MacDermot, K D; McKee, Shane; Magee, Alex; Man, Stella A. de; Moreau, Yves; Morice‐Picard, Fanny; Obersztyn, Ewa; Pilch, Jacek; Rosser, Elizabeth C.; Shannon, Nora; Stolte‐Dijkstra, Irene; Dijck, Patrick Van; Vilain, Catheline; Vogels, Annick; Wakeling, Emma; Wieczorek, Dagmar; Wilson, Louise C.; Zuffardi, Orsetta; Kampen, Antoine H. C. van; Devriendt, Koenraad; Hennekam, Raoul C. M.; Vermeesch, Joris Robert

doi:10.1038/ng.1105

Cited by 214 publications

(211 citation statements)

References 25 publications

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“…Some studies have revealed that Smarca4 is essential for heart development in mouse and zebrafish embryogenesis, whereas Smarca2 appears to be dispensable 34,35 . In humans, the role of SMARCA2 in cardiogenesis is unclear; however, several independent exome sequencing projects have identified de novo mutations in SMARCA2 that are associated with two congenital syndromes that include cardiac defects: Coffin-Siris syndrome and Nicolaides-Baraitser syndrome 36,37 .…”

Section: Discussionmentioning

confidence: 99%

Association analysis identifies new risk loci for congenital heart disease in Chinese populations

et al. 2015

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Our previous genome-wide association study (GWAS) identified two susceptibility loci for congenital heart disease (CHD) in Han Chinese. Here we identify additional loci by testing promising associations in an extended 3-stage validation consisting of 6,053 CHD cases and 7,410 controls. We find GW significant (Po5.0 Â 10 À 8 ) evidence of 4 additional CHD susceptibility loci at 4q31.22 (rs1400558, upstream of EDNRA, P all ¼ 1.63 Â 10 À 9 ), 9p24.2 (rs7863990, close to SMARCA2, P all ¼ 3.71 Â 10 À 14 ), 12q24.13 (rs2433752, upstream of TBX3 and TBX5, P all ¼ 1.04 Â 10 À 10 ) and 20q12 (rs490514, in PTPRT, P all ¼ 1.20 Â 10 À 13 ). Moreover, the data from previous European GWAS supports that rs490514 is associated with the risk of CHD (P ¼ 3.40 Â 10 À 3 ). These results enhance our understanding of CHD susceptibility.

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Section: Discussionmentioning

confidence: 99%

Association analysis identifies new risk loci for congenital heart disease in Chinese populations

et al. 2015

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“…Recently, heterozygous nonsynonymous mutations or partial deletions in SMARCA2 were identified as the cause of Nicolaides-Baraitser syndrome, an autosomal dominant condition with syndromic ID. 30 The third probably causal abnormality was a de novo deletion on chromosome 3q29. The 3q29 microdeletion syndrome has been recently described as a new syndrome, probably caused by nonallelic homologous recombination.…”

Section: Discussionmentioning

confidence: 99%

Prospective diagnostic analysis of copy number variants using SNP microarrays in individuals with autism spectrum disorders

et al. 2013

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Copy number variants (CNVs) have repeatedly been found to cause or predispose to autism spectrum disorders (ASDs). For diagnostic purposes, we screened 194 individuals with ASDs for CNVs using Illumina SNP arrays. In several probands, we also analyzed candidate genes located in inherited deletions to unmask autosomal recessive variants. Three CNVs, a de novo triplication of chromosome 15q11-q12 of paternal origin, a deletion on chromosome 9p24 and a de novo 3q29 deletion, were identified as the cause of the disorder in one individual each. An autosomal recessive cause was considered possible in two patients: a homozygous 1p31.1 deletion encompassing PTGER3 and a deletion of the entire DOCK10 gene associated with a rare hemizygous missense variant. We also identified multiple private or recurrent CNVs, the majority of which were inherited from asymptomatic parents. Although highly penetrant CNVs or variants inherited in an autosomal recessive manner were detected in rare cases, our results mainly support the hypothesis that most CNVs contribute to ASDs in association with other CNVs or point variants located elsewhere in the genome. Identification of these genetic interactions in individuals with ASDs constitutes a formidable challenge.

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“…Patients NL39 and NL66 both had a CNV in chromosomal band 9p24.3. The smallest overlap region contained a single gene, SMARCA2, which has recently been associated with Nicolaides-Baraitser syndrome 14 ( Supplementary Figure 2). However, duplications in other parts of this gene have been found as benign variants, raising issues regarding the pathogenicity of these variants.…”

Section: Novel Recurrent Cnvsmentioning

confidence: 99%

Structural genomic variation in childhood epilepsies with complex phenotypes

et al. 2013

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A genetic contribution to a broad range of epilepsies has been postulated, and particularly copy number variations (CNVs) have emerged as significant genetic risk factors. However, the role of CNVs in patients with epilepsies with complex phenotypes is not known. Therefore, we investigated the role of CNVs in patients with unclassified epilepsies and complex phenotypes. A total of 222 patients from three European countries, including patients with structural lesions on magnetic resonance imaging (MRI), dysmorphic features, and multiple congenital anomalies, were clinically evaluated and screened for CNVs. MRI findings including acquired or developmental lesions and patient characteristics were subdivided and analyzed in subgroups. MRI data were available for 88.3% of patients, of whom 41.6% had abnormal MRI findings. Eighty-eight rare CNVs were discovered in 71 out of 222 patients (31.9%). Segregation of all identified variants could be assessed in 42 patients, 11 of which were de novo. The frequency of all structural variants and de novo variants was not statistically different between patients with or without MRI abnormalities or MRI subcategories. Patients with dysmorphic features were more likely to carry a rare CNV. Genome-wide screening methods for rare CNVs may provide clues for the genetic etiology in patients with a broader range of epilepsies than previously anticipated, including in patients with various brain anomalies detectable by MRI. Performing genome-wide screens for rare CNVs can be a valuable contribution to the routine diagnostic workup in patients with a broad range of childhood epilepsies.

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Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome

Cited by 214 publications

References 25 publications

Association analysis identifies new risk loci for congenital heart disease in Chinese populations

Association analysis identifies new risk loci for congenital heart disease in Chinese populations

Prospective diagnostic analysis of copy number variants using SNP microarrays in individuals with autism spectrum disorders

Structural genomic variation in childhood epilepsies with complex phenotypes

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