Cornelia de Lange syndrome, related disorders, and the Cohesin complex: Abstracts from the 8th biennial scientific and educational symposium 2018

Kline, Antonie D.; Krantz, Ian D.; Bando, Masashige; Shirahige, Katsuhiko; Chea, Stephenson; Sakata, Toyonori; Rao, Suhas S.P.; Dorsett, Dale; Singh, Vijay Pratap; Gerton, Jennifer L.; Horsfield, Julia A.; Calof, Anne L.; Katz, Olivia; Grados, Marco A.; Raible, Sarah E.; Barañano, Kristin W.; Lyon, Gholson J.; Musio, Antonio; Carrico, Cheri S.; Clemens, Douglas K.; Caudill, Patti; Massa, Valentina; McGill, Bryan E.; Dommestrup, Aila K.; O’Connor, Julia T.; Haaland, Richard E.

doi:10.1002/ajmg.a.61108

Cited by 2 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Overall, since the cohesin complex is involved in regulating gene expression during embryogenesis, cohesinopathies are characterized by a variety of developmental defects, including growth and mental delay, limb deformities, and craniofacial anomalies [ 16 ]. In particular, intellectual disability is related to impairment in neuronal development and transcriptional regulation (including initiation, general transcription, elongation, pausing, backtracking, processing, termination, and associated epigenetic modifications) [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Cohesin Mutations Induce Chromatin Conformation Perturbation of the H19/IGF2 Imprinted Region and Gene Expression Dysregulation in Cornelia de Lange Syndrome Cell Lines

et al. 2021

View full text Add to dashboard Cite

Traditionally, Cornelia de Lange Syndrome (CdLS) is considered a cohesinopathy caused by constitutive mutations in cohesin complex genes. Cohesin is a major regulator of chromatin architecture, including the formation of chromatin loops at the imprinted IGF2/H19 domain. We used 3C analysis on lymphoblastoid cells from CdLS patients carrying mutations in NIPBL and SMC1A genes to explore 3D chromatin structure of the IGF2/H19 locus and evaluate the influence of cohesin alterations in chromatin architecture. We also assessed quantitative expression of imprinted loci and WNT pathway genes, together with DMR methylation status of the imprinted genes. A general impairment of chromatin architecture and the emergence of new interactions were found. Moreover, imprinting alterations also involved the expression and methylation levels of imprinted genes, suggesting an association among cohesin genetic defects, chromatin architecture impairment, and imprinting network alteration. The WNT pathway resulted dysregulated: canonical WNT, cell cycle, and WNT signal negative regulation were the most significantly affected subpathways. Among the deregulated pathway nodes, the key node of the frizzled receptors was repressed. Our study provides new evidence that mutations in genes of the cohesin complex have effects on the chromatin architecture and epigenetic stability of genes commonly regulated by high order chromatin structure.

show abstract

Section: Introductionmentioning

confidence: 99%

Cohesin Mutations Induce Chromatin Conformation Perturbation of the H19/IGF2 Imprinted Region and Gene Expression Dysregulation in Cornelia de Lange Syndrome Cell Lines

et al. 2021

View full text Add to dashboard Cite

show abstract

“…We also clinically scored the features based on the recent international consensus for CdLS (Kline et al, 2018). A preliminary summary of this study was previously reported (Kline et al, 2019). New findings of premature breast, axillary hair and pubic hair development were noted recently, prompting a search for other conditions with intractable seizures.…”

Section: Smc1a Loss‐of‐function Variants With Premature Thelarche Adr...mentioning

confidence: 80%

“…We also clinically scored the features based on the recent international consensus for CdLS . A preliminary summary of this study was previously reported (Kline et al, 2019).…”

Section: Genes or Misallocation Of Progenitors?mentioning

confidence: 94%

Cornelia de Lange syndrome and the Cohesin complex: Abstracts from the 9th Biennial Scientific and Educational Virtual Symposium 2020

Oliver

Groves

Hansen

et al. 2021

American J of Med Genetics Pt A

Self Cite

View full text Add to dashboard Cite

Cornelia de Lange syndrome (CdLS) is a spectrum disorder due to variants in genes of the cohesin protein complex. The following abstracts are from the Cornelia de Lange Syndrome Scientific and Educational Symposium held virtually in October 2020. Aspects of behavior, including autistic features, impulsivity, adaptive skills, executive function, and anxiety are described. Applied behavioral analysis is a promising approach for autism, and an N‐acetylcysteine trial is proposed. Children below 6 years with CdLS have an increased number of and further travel to medical providers, with insurance type comprising a significant barrier. Speech, language, and feeding abilities fall significantly below expectations for age in CdLS. Augmentative alternative communication can yield potential barriers as well as interesting benefits. Developmentally, studies in animal models further elucidate the mechanisms and roles of cohesin: link with mediator transcriptional complex; facilitation of enhancer‐promoter communication; regulation of gene expression; allocation of cells to germ layers; and repair of spontaneous DNA damage in placental cells. Genome and RNA sequencing can help identify the molecular cause in the 20% of individuals with suspected CdLS and negative testing. The phenotypes in individuals with variants in the SMC1A gene are distinct, and that with intractable seizures has been further evaluated. AMA CME credits provided by GBMC, Baltimore, MD. All studies approved by an ethics committee.

show abstract

Cornelia de Lange syndrome, related disorders, and the Cohesin complex: Abstracts from the 8th biennial scientific and educational symposium 2018

Cited by 2 publications

References 0 publications

Cohesin Mutations Induce Chromatin Conformation Perturbation of the H19/IGF2 Imprinted Region and Gene Expression Dysregulation in Cornelia de Lange Syndrome Cell Lines

Cohesin Mutations Induce Chromatin Conformation Perturbation of the H19/IGF2 Imprinted Region and Gene Expression Dysregulation in Cornelia de Lange Syndrome Cell Lines

Cornelia de Lange syndrome and the Cohesin complex: Abstracts from the 9th Biennial Scientific and Educational Virtual Symposium 2020

Contact Info

Product

Resources

About