Mutations in SWI/SNF chromatin remodeling complex gene ARID1B cause Coffin-Siris syndrome

Santen, Gijs W.E.; Aten, Emmelien; Sun, Yu; Almomani, Rowida; Gilissen, Christian; Nielsen, Maartje; Kant, Sarina G.; Snoeck, I.; Peeters, Els; Hilhorst‐Hofstee, Yvonne; Wessels, Marja W.; Hollander, Nicolette S. den; Ruivenkamp, Claudia; Ommen, Gert‐Jan B. van; Breuning, Martijn H.; Dunnen, Johan T. den; Haeringen, Arie van; Kriek, Marjolein

doi:10.1038/ng.2217

Cited by 322 publications

(292 citation statements)

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“…8 So far, only nonsense and frameshift mutations in ARID1B as well as whole-gene deletions have been identified in patients with CSS. [4][5][6]12 In our patient, a 1-bp deletion c.1584delG in ARID1B predicted to cause a frameshift and a premature termination of the protein p.(Leu528Phefs*65) was identified. This alteration most likely results in loss-of-function of the protein, suggesting haploinsufficiency as a disease-causing mechanism.…”

Section: Discussionmentioning

confidence: 60%

“…3 CSS is now classified as a BAF (also known as SWI/SNF) complex disorder, 4 as several syndrome-related genes that encode subunits of the BAF complex -ARID1A, ARID1B, SMARCA4, SMARCB1, SMARCA2 and SMARCE1 -have been identified. [5][6][7] The BAF complex modulates chromatin structure and has important roles in transcription, cell differentiation, DNA repair and tumor suppression as reviewed by Hargreaves and Crabtree. 8 Heterozygous mutations of these genes are inherited in an autosomal dominant manner, but they usually result from a de novo mutation.…”

Section: Introductionmentioning

confidence: 99%

“…[4][5][6][7][9][10][11][12][13][14] Most of them had a clinical diagnosis of CSS, but it can be due to careful clinical preselection for molecular study. [4][5][6][7]9 In some patients, the mutation in ARID1B was found when searching the cause of unexplained intellectual disability (ID) without CSS diagnosis. 11,12 In this study, we report a novel ARID1B mutation identified by whole-exome sequencing in a patient with clinical features characteristic to CSS.…”

Section: Introductionmentioning

confidence: 99%

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Coffin–Siris Syndrome with obesity, macrocephaly, hepatomegaly and hyperinsulinism caused by a mutation in the ARID1B gene

et al. 2014

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Section: Discussionmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Coffin–Siris Syndrome with obesity, macrocephaly, hepatomegaly and hyperinsulinism caused by a mutation in the ARID1B gene

et al. 2014

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“…4). ARID1B causes Coffin Siris syndrome (Santen et al, 2012), a syndrome associated with ACC. De novo intragenic deletions of ARID1B have been reported in individuals with either ACC or autism (Backx et al, 2011;Halgren et al, 2012) suggesting ARID1B a likely candidate gene for ACC.…”

Section: Discussionmentioning

confidence: 99%

Array‐based molecular karyotyping in fetal brain malformations: Identification of novel candidate genes and chromosomal regions

Krutzke

Engels

Hofmann

et al. 2015

Birth Defects Research

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BACKGROUND: For the majority of congenital brain malformations, the underlying cause remains unknown. Recent studies have implicated rare copy number variations (CNVs) in their etiology. METHODS: Here, we used array-based molecular karyotyping to search for causative CNVs in 33 fetuses of terminated pregnancies with prenatally detected brain malformations and additional extracerebral anomalies. RESULTS: In 11 fetuses, we identified 15 CNVs (0.08 Mb to 29.59 Mb), comprising four duplications and eleven deletions. All larger CNVs (> 5 Mb) had also been detected by prenatal conventional karyotyping. None of these CNVs was present in our 1307 healthy in-house controls (frequency < 0.0008). Among these CNVs, we prioritized six chromosomal regions (1q25.1, 5q35.1, 6q25.3-qter, 11p14.3, 15q11.2-q13.1, 18q21.1) due to their previous association with human brain malformations or owing to the presence of a single gene expressed in human brain. Prioritized genes within these regions were UBTD2, SKA1, SVIP, and, most convincingly, GPR52. However, re-sequencing of GPR52 in 100 samples from fetuses with brain malformations or patients with intellectual disability and brain malformations revealed no disease-causing mutation. CONCLUSION: Our study suggests chromosomal regions 1q25.1, 5q35.1, 6q25.3-qter, 11p14.3, 15q11.2-q13.1, and 18q21.1 to be involved in human brain development. Within three of these regions, we suggest UBTD2, GPR52, and SKA1 as possible candidate genes. Because the overall detection rate of array-based molecular karyotyping was slightly higher (23%) than that of conventional prenatal karyotyping (20%), we suggest it's use for prenatal diagnostic testing in fetuses with nonisolated brain malformations.

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“…For example, different mutations in SWI/SNF chromatin remodelling complex were reported to cause Coffin-Siris syndrome [14,15], Nicolaides-Baraitser syndrome [16], and cancers [17,18]. Aberration in mitochondrial complex-I NADH dehydrogenase activity could profoundly enhance the aggressiveness of human breast cancer cells, while therapeutic normalization of the NAD+/NADH balance could inhibit metastasis and prevent disease progression [19].…”

Section: Introductionmentioning

confidence: 99%

Prioritizing protein complexes implicated in human diseases by network optimization

et al. 2014

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BackgroundThe detection of associations between protein complexes and human inherited diseases is of great importance in understanding mechanisms of diseases. Dysfunctions of a protein complex are usually defined by its member disturbance and consequently result in certain diseases. Although individual disease proteins have been widely predicted, computational methods are still absent for systematically investigating disease-related protein complexes.ResultsWe propose a method, MAXCOM, for the prioritization of candidate protein complexes. MAXCOM performs a maximum information flow algorithm to optimize relationships between a query disease and candidate protein complexes through a heterogeneous network that is constructed by combining protein-protein interactions and disease phenotypic similarities. Cross-validation experiments on 539 protein complexes show that MAXCOM can rank 382 (70.87%) protein complexes at the top against protein complexes constructed at random. Permutation experiments further confirm that MAXCOM is robust to the network structure and parameters involved. We further analyze protein complexes ranked among top ten for breast cancer and demonstrate that the SWI/SNF complex is potentially associated with breast cancer.ConclusionsMAXCOM is an effective method for the discovery of disease-related protein complexes based on network optimization. The high performance and robustness of this approach can facilitate not only pathologic studies of diseases, but also the design of drugs targeting on multiple proteins.

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Mutations in SWI/SNF chromatin remodeling complex gene ARID1B cause Coffin-Siris syndrome

Cited by 322 publications

References 13 publications

Coffin–Siris Syndrome with obesity, macrocephaly, hepatomegaly and hyperinsulinism caused by a mutation in the ARID1B gene

Coffin–Siris Syndrome with obesity, macrocephaly, hepatomegaly and hyperinsulinism caused by a mutation in the ARID1B gene

Array‐based molecular karyotyping in fetal brain malformations: Identification of novel candidate genes and chromosomal regions

Prioritizing protein complexes implicated in human diseases by network optimization

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