Natural history of aging in Cornelia de Lange syndrome

Kline, Antonie D.; Grados, Marco A.; Sponseller, Paul D.; Levy, Howard P.; Blagowidow, Natalie; Schoedel, Christianne; Rampolla, Joni; Clemens, Douglas K.; Krantz, Ian D.; Kimball, Amy; Pichard, Carmen P.; Tuchman, David N.

doi:10.1002/ajmg.c.30137

Cited by 134 publications

(198 citation statements)

References 46 publications

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“…Kline et al 16 presented a review of 59 North American adolescents and adults, ascertained through a multidisciplinary clinic with a mean age of 17 and 9 months (range 11-50 years) years. The majority of individuals were diagnosed in childhood.…”

Section: Cdls In Adolescents and Adultsmentioning

confidence: 99%

Cornelia de Lange Syndrome

Liu

Baynam

2010

Advances in Experimental Medicine and Biology

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C ornelia de Lange syndrome (CdLS) (OMIM # 122470, #300590 and #610759) is an autosomal dominant disorder that is classically characterized by typical facial features, growth and mental retardation, upper limb defects, hirsutism, gastrointestinal and other visceral system involvement. Heterozygous mutations in the cohesin regulator, NIPBL, or the cohesin structural components SMC1A and SMC3, have been identified in approximately 65% of individuals with CdLS. Cohesin regulates sister chromatid cohesion during the mitotis and meiosis. In addition, cohesin has been demonstrated to play a critical role in the regulation of gene expression. Furthermore, multiple proteins in the cohesin pathway are also involved in additional fundamental biological events such as double strand DNA break repair, chromatin remodeling and maintaining genomic stability. Here, we will discuss the biology of cohesin and its associated factors, with emphasis on the clinical manifestations of CdLS and mechanistic studies of the CdLS related proteins.

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Section: Cdls In Adolescents and Adultsmentioning

confidence: 99%

Cornelia de Lange Syndrome

Liu

Baynam

2010

Advances in Experimental Medicine and Biology

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“…However, there was a report of another female patient without arched eyebrows and synophrys, similar to the present patient. In addition, Kline et al found that the facies of CdLS patients could change with age [18]. Therefore, it is likely that the facies of these two female patients without synophrys and arched eyebrows may become more typical with advancing age.…”

Section: Discussionmentioning

confidence: 99%

A Functional Mutation in HDAC8 Gene as Novel Diagnostic Marker for Cornelia De Lange Syndrome

Gao¹,

Huang²,

Fan³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Cornelia de Lange Syndrome (CdLS) is a rare genetic disorder classically characterized by distinctive facies, growth retardation, intellectual disability, feeding difficulties, and multiple organ system anomalies. Previously, the diagnosis of CdLS was based mainly on identifying the typical phenotype in patients. However, with the advances in clinical molecular genetic diagnostic techniques, more patients, especially patients with milder phenotypes, are being diagnosed from detecting pathogenic mutation. Methods: Pathogenic mutation in a female patient with a milder phenotype was detected using whole-exome sequencing (WES), and was further characterized using bioinformatic analysis and in vitro functional experiments, including X-chromosome inactivation analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and enzyme activity assay. Results: This patient was found to harbor a novel missense mutation (c.806T>G, p.I269R) in the coding region of the HDAC8 gene, which was predicted to be pathogenic. Compared with other CdLS patients with HDAC8 mutation, the patient lacked typical facies, including synophrys and arched eyebrows. In vitro functional experiments showed the presence of skewed X-chromosome inactivation. Furthermore, the novel mutation decreased the dissolubility and enzymatic activity of HDAC8 protein. Conclusions: The present study identified a novel missense mutation (c.806T>G, p.I269R) in the HDAC8 gene leading to CdLS, which not only provided strong evidence for diagnosis in this present patient, but also expanded the spectrum of pathogenic mutations for CdLS.

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“…In most cases, radiological scans were not available for review, and therefore, the true incidence of structural brain abnormality is not known. (Kline et al, 2007b).…”

Section: Discussionmentioning

confidence: 99%

Cornelia de Lange syndrome (CdLS): prenatal and autopsy findings

et al. 2009

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Cornelia de Lange Syndrome (CdLS) is a multisystem disorder characterized by somatic defects and mental retardation. Prenatal diagnosis of this severe condition is difficult in view of the non-specific ultrasound abnormalities. We report three cases with prenatally suspected CdLS based on the ultrasound findings as well as low PAPP-A detected on first trimester screening in one case, and the results of the autopsy and the NIPBL gene mutation analysis.

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Natural history of aging in Cornelia de Lange syndrome

Cited by 134 publications

References 46 publications

Cornelia de Lange Syndrome

Cornelia de Lange Syndrome

A Functional Mutation in HDAC8 Gene as Novel Diagnostic Marker for Cornelia De Lange Syndrome

Cornelia de Lange syndrome (CdLS): prenatal and autopsy findings

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