Genetic abnormalities in a large cohort of Coffin–Siris syndrome patients

Sekiguchi, Futoshi; Tsurusaki, Yoshinori; Okamoto, Nobuhiko; Teik, Keng Wee; Mizuno, Seiji; Suzumura, Hiroshi; Isidor, Bertrand; Ong, Winnie Peitee; Haniffa, Muzhirah; White, Susan; Matsuo, Mari; Saito, Kayoko; Phadke, Shubha R.; Kosho, Tomoki; Yap, Patrick; Goyal, Manisha; Clarke, Lorne; Sachdev, Rani; McGillivray, George; Leventer, Richard J.; Patel, Chirag; Yamagata, Takanori; Osaka, Hitoshi; Hisaeda, Yoshiya; Ohashi, Hirofumi; Shimizu, Kenji; Nagasaki, Keisuke; Hamada, Junpei; Dateki, Sumito; Sato, Takashi; Chinen, Yoshiaki; Awaya, Tomonari; Katô, Takeo; Iwanaga, Kougoro; Kawai, Masahiko; Matsuoka, Takashi; Shimoji, Yoshikazu; Tan, Tiong Yang; Kapoor, Seema; Gregersen, Nerine; Rossi, Massimiliano; Marie-Laure, Mathieu; McGregor, Lesley; Oishi, Kimihiko; Mehta, Lakshmi; Gillies, Greta; Lockhart, Paul J.; Pope, Kate; Shukla, Anju; Girisha, Katta M.; Abdel-Salam, Ghada M H; Mowat, David; Coman, David; Kim, Ok Hwa; Cordier, Marie Pierre; Gibson, Kate; Milunsky, Jeff M.; Liebelt, Jan; Cox, Helen; Chehadeh, Salima El; Toutain, Annick; Saida, Ken; Aoi, Hiromi; Minase, Gaku; Tsuchida, Naomi; Iwama, Kazuhiro; Uchiyama, Yuri; Suzuki, Toshifumi; Hamanaka, Kohei; Azuma, Yoshiteru; Fujita, Atsushi; Imagawa, Eri; Koshimizu, Eriko; Takata, Atsushi; Mitsuhashi, Satomi; Miyatake, Satoko; Mizuguchi, Takeshi; Miyake, Noriko; Matsumoto, Naomichi

doi:10.1038/s10038-019-0667-4

Cited by 52 publications

(41 citation statements)

References 42 publications

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“…The Coffin-Siris syndromes (CSS) are a genetically heterogeneous group of congenital disorders characterized by intellectual disability, coarse facial features, hypoplastic or absent fifth fingernails or toenails, and multiple other anomalies including ocular features [3]. The various forms of Coffin-Siris syndrome have been shown to be caused by mutations in 11 different genes encoding subunits of a chromatin remodelling factor, the SWI/SNF (SWItch/Sucrose Non-Fermentable) complex.…”

Section: Introductionmentioning

confidence: 99%

First observation of secondary childhood glaucoma in Coffin-Siris syndrome: a case report and literature review

et al. 2021

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Background Severe congenital ophthalmological malformations and glaucoma might be an important occasional feature in patients with Coffin-Siris syndrome (CSS), especially Coffin-Siris syndrome 9 (CSS9, OMIM #615866) caused by SOX11 mutation. Recently, primary (open-angle) glaucoma was described in two children with the most common form of Coffin-Siris syndrome, CSS1 (OMIM #135900) by ARID1B (AT-rich interaction domain-containing protein 1B) gene mutation. In this article, we present the first report of glaucoma with Coffin-Siris syndrome 9 as well as the first report of secondary glaucoma with any form of Coffin-Siris syndrome. These findings indicate that secondary glaucoma is an occasional finding in patients with Coffin-Siris syndrome. Case presentation A child with secondary childhood glaucoma and additional ocular manifestations was evaluated and treated at the childhood glaucoma centre in Mainz, Germany. Examination under general anaesthesia revealed ocular anterior segment dysgenesis (ASD) (Peters type iridocorneal dysgenesis) in combination with congenital limbal stem cell deficiency (LSCD), aniridia, and cataract. The patient also had multiple other congenital anomalies and severe developmental delay. To explain his combination of anomalies, molecular genetic analysis from peripheral blood was performed in late 2018 and early 2019. Following normal findings with a panel diagnostic of 18 genes associated with congenital glaucoma, whole exome sequencing was performed and revealed a novel likely pathogenic heterozygous variant c.251G>T, p.(Gly84Val) in the SOX11 gene (SRY-related HMG-box gene 11). The variant had occurred de novo. Thus, the multiple congenital anomalies and developmental delay of the patient represented Coffin-Siris syndrome 9 (CSS9, OMIM #615866). Conclusions When eye diseases occur in combination with other systemic features, genetic analysis can be seminal. Results indicate that glaucoma is an occasional feature of patients with Coffin-Siris syndrome. As early treatment may improve the visual outcome of patients with glaucoma, we suggest that patients with Coffin-Siris syndrome should receive specific ophthalmological screening.

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Section: Introductionmentioning

confidence: 99%

First observation of secondary childhood glaucoma in Coffin-Siris syndrome: a case report and literature review

et al. 2021

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“…Heterozygous mutations in SMARCA4 have thus far been reported in at least 20 patients with a CSS phenotype [Kosho et al, 2014a;Dsouza et al, 2019;Sekiguchi et al, 2019], and were all non-truncating (either missense or inframe deletions), leading to gain-of-function or negativedominant effects. Small in-frame deletions have also been reported [Tsurusaki et al, 2012[Tsurusaki et al, , 2014Kosho et al, 2014b].…”

Section: Discussionmentioning

confidence: 99%

“…Reports on CNVs affecting SMARCA4 are rare. In the most recent study, Sekiguchi et al [2019] tested a cohort of more than 200 patients with CSS for single nucleotide variants as well as CNVs on all genes so far suspected to contribute to CSS, with no detected CNVs affecting the SMARCA4 gene. Haberlandt et al [2012] reported on a 4-year-old boy with ID, minor dysmorphisms, and febrile seizures that carried a de novo deletion of 834.2 kb in 19p13.2 encompassing 32 genes, discussing a potential role of SMARCA4 haploinsufficiency.…”

Section: Discussionmentioning

confidence: 99%

“…Heterozygous mutations in SMARCA4 have thus far been reported in at least 20 patients with CSS phenotypes [Kosho et al, 2014a;Dsouza et al, 2019;Sekiguchi et al, 2019]. Small in-frame deletions have also been reported [Tsurusaki et al, 2012[Tsurusaki et al, , 2014Kosho et al, 2014b]; however, reports on focal copy number variants (CNVs) of 19p13.2 affecting SMARCA4 are rare and typically include additional genes due to the high gene density of the specific chromosomal region [Haberlandt et al, 2012].…”

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confidence: 99%

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Coffin-Siris Syndrome 4-Related Spectrum in a Young Woman Caused by a Heterozygous SMARCA4 Deletion Detected by High-Resolution aCGH

et al. 2020

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Coffin-Siris Syndrome 4 is an autosomal dominant congenital malformation syndrome caused by heterozygous mutations in the SMARCA4 gene with its main features being intellectual disability, developmental delay, behavioral abnormalities, and hypoplastic or absent fifth fingernails and fifth distal phalanges. Here, we report a young woman with developmental delay, moderate intellectual disability, and bilateral sensorineural hearing loss, referred for genetic testing. High-resolution chromosomal microarray analysis identified a 428-kb deletion in chromosome 19 which included the SMARCA4 gene. We conclude that haploinsufficiency of SMARCA4 may be a valid pathophysiological mechanism leading to milder Coffin-Siris syndrome phenotypes.

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“…Although the last study performed on a large cohort of CSS patients proved that they carry the missense mutation in SMARCA4 (BRG1 encoding gene) gene but not in BRM-encoding SMARCA2 gene. In some CSS patients, duplication of the SMARCA2 gene was detected [34]. On the other hand, missense mutations in SMARCA2 were detected in NCBRS patients [35].…”

Section: Main Textmentioning

confidence: 99%

BRM: the core ATPase subunit of SWI/SNF chromatin-remodelling complex—a tumour suppressor or tumour-promoting factor?

Jancewicz

Siedlecki

Sarnowski

et al. 2019

Epigenetics & Chromatin

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BRM (BRAHMA) is a core, SWI2/SNF2-type ATPase subunit of SWI/SNF chromatin-remodelling complex (CRC) involved in various important regulatory processes including development. Mutations in SMARCA2, a BRM-encoding gene as well as overexpression or epigenetic silencing were found in various human diseases including cancer. Missense mutations in SMARCA2 gene were recently connected with occurrence of Nicolaides–Baraitser genetics syndrome. By contrast, SMARCA2 duplication rather than mutations is characteristic for Coffin–Siris syndrome. It is believed that BRM usually acts as a tumour suppressor or a tumour susceptibility gene. However, other studies provided evidence that BRM function may differ depending on the cancer type and the disease stage, where BRM may play a role in the disease progression. The existence of alternative splicing forms of SMARCA2 gene, leading to appearance of truncated functional, loss of function or gain-of-function forms of BRM protein suggest a far more complicated mode of BRM-containing SWI/SNF CRCs actions. Therefore, the summary of recent knowledge regarding BRM alteration in various types of cancer and highlighting of differences and commonalities between BRM and BRG1, another SWI2/SNF2 type ATPase, will lead to better understanding of SWI/SNF CRCs function in cancer development/progression. BRM has been recently proposed as an attractive target for various anticancer therapies including the use of small molecule inhibitors, synthetic lethality induction or proteolysis-targeting chimera (PROTAC). However, such attempts have some limitations and may lead to severe side effects given the homology of BRM ATPase domain to other ATPases, as well as due to the tissue-specific appearance of BRM- and BRG1-containing SWI/SNF CRC classes. Thus, a better insight into BRM-containing SWI/SNF CRCs function in human tissues and cancers is clearly required to provide a solid basis for establishment of new safe anticancer therapies.

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Genetic abnormalities in a large cohort of Coffin–Siris syndrome patients

Cited by 52 publications

References 42 publications

First observation of secondary childhood glaucoma in Coffin-Siris syndrome: a case report and literature review

First observation of secondary childhood glaucoma in Coffin-Siris syndrome: a case report and literature review

Coffin-Siris Syndrome 4-Related Spectrum in a Young Woman Caused by a Heterozygous <b><i>SMARCA4</i></b> Deletion Detected by High-Resolution aCGH

BRM: the core ATPase subunit of SWI/SNF chromatin-remodelling complex—a tumour suppressor or tumour-promoting factor?

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