Clinical utility gene card for: Cornelia de Lange syndrome

Ramos, Feliciano J.; Puisac, Beatriz; Baquero-Montoya, Carolina; Gil-Rodríguez, Ma Concepción; Bueno, Inés; Deardorff, Matthew A.; Hennekam, Raoul C. M.; Kaiser, Frank J.; Krantz, Ian D.; Musio, Antonio; Selicorni, Angelo; FitzPatrick, David R.; Pié, Juan

doi:10.1038/ejhg.2014.270

Cited by 39 publications

(34 citation statements)

References 26 publications

(29 reference statements)

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“…The NIPBL mutations are reported to be the pathogenic cause in approximately 70-80% of CdLS cases [3,13]. Three de novo heterozygous NIPBL mutations have been identified in our patients, which is consistent with the previous studies, in which 99% of NIPBL-related CdLS cases are caused by de novo autosomal heterozygous pathogenic mutations [1,9,21].…”

Section: Discussionsupporting

confidence: 92%

“…Cohesin is an essential protein complex for the chromosome segregation in dividing cells, DNA repair mechanism, and gene regulations [11,12]. Close to 70-80% of CdLS cases are associated with the mutations in the NIPBL gene [3,13]. The NIPBL gene encodes for delangin, an ortholog of Scc2 protein in Drosophila, which, coupled with Scc4 protein, regulates the loading of the cohesin ring onto chromatin [1,11].…”

Section: Introductionmentioning

confidence: 99%

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De novo NIPBL Mutations in Vietnamese Patients with Cornelia de Lange Syndrome

et al. 2020

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Cornelia de Lange Syndrome (CdLS) is a rare congenital genetic disease causing abnormal unique facial phenotypes, several defects in organs and body parts, and mental disorder or intellectual disorder traits. Main causes of CdLS have been reported as variants in cohesin complex genes, in which mutations in the NIPBL gene have been estimated to account for up to 80%. Our study included three Vietnamese patients with typical CdLS phenotypes. Whole exome sequencing revealed two known heterozygous mutations c.6697G>A (p.Val2233Met) and c.2602C>T (p.Arg868X), and a novel heterozygous mutation c.4504delG (p.Val1502fsX87) in the NIPBL gene of the three patients. In silico analyses of the identified mutations predicted possible damaging and truncating effects on the NIPBL protein. Inherited analyses in the patients' families showed that all of the mutations are de novo. Our results lead a definitive diagnosis of patients with CdLS and expand the spectrum of mutations in the NIPBL gene. These findings also confirm whole exome sequencing is an efficient tool for genetic screening of CdLS.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

De novo NIPBL Mutations in Vietnamese Patients with Cornelia de Lange Syndrome

et al. 2020

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“…The worldwide incidence of CdLS is reported to range from 1 to 3 per 30, 000 births [1]. However, in view of the wide clinical variability and limited clinical knowledge about the disease, the actual global incidence of CdLS may be higher.…”

Section: Introductionmentioning

confidence: 96%

“…Thus, it is difficult to make an accurate diagnosis in patients with milder phenotypes based on phenotypic features alone. With the development of clinical molecular genetic diagnostic techniques however, such patients can now be diagnosed by detecting mutations in CdLS-related genes, mainly including NIPBL, SMC1A, SMC3, RAD21, and HDAC8 [1].…”

Section: Introductionmentioning

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 ‘classical’ CdLS, de novo mutations in NIPBL are found in around 50% of cases. More recently, mutations in other genes encoding other structural or regulatory components of the cohesion ring, SMC1A, SMC3, HDAC8 and RAD21, have been found in patients with ‘mild’ CdLS 2. The phenotypic and genotypic correlations and wide spectrum of clinical features are well described in the literature 3–6.…”

Section: Introductionmentioning

confidence: 98%

Cornelia de Lange syndrome due to mosaic NIPBL mutation: antenatal presentation with sacrococcygeal teratoma

Banait¹,

Fenton

Splitt

2015

BMJ Case Reports

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A male infant at 36 weeks gestation was born by section. At 20 weeks of gestation, congenital diaphragmatic hernia and sacrococcygeal teratoma had been seen on ultrasound. At birth, the infant had features suggestive of Cornelia de Lange syndrome (CdLS). He remained hypoxic despite aggressive ventilatory manoeuvres and was palliated. At postmortem, the lungs were hypoplastic. In CdLS, mutations in NIPBL are found in around 50% of cases. Mutation analysis, including multiplex ligation dependent probe amplification of the NIPBL gene from the DNA extracted from peripheral blood lymphocytes was negative, but microarray comparative genomic hybridisation on DNA from skin fibroblast showed a 0.13Mb deletion on chromosome 5p13. The deleted region includes exons 42-47 of the NIPBL gene. It is important to perform NIBPL mutation analysis on DNA from more than one tissue when testing for CdLS.

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Clinical utility gene card for: Cornelia de Lange syndrome

Cited by 39 publications

References 26 publications

De novo NIPBL Mutations in Vietnamese Patients with Cornelia de Lange Syndrome

De novo NIPBL Mutations in Vietnamese Patients with Cornelia de Lange Syndrome

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

Cornelia de Lange syndrome due to mosaic NIPBL mutation: antenatal presentation with sacrococcygeal teratoma

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