scholarly journals Clinical relevance of postzygotic mosaicism in Cornelia de Lange syndrome and purifying selection of NIPBL variants in blood

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ana Latorre-Pellicer ◽  
Marta Gil-Salvador ◽  
Ilaria Parenti ◽  
Cristina Lucia-Campos ◽  
Laura Trujillano ◽  
...  
Keyword(s):  
Somatic Mosaicism ◽  
Purifying Selection ◽  
Mosaic Disease ◽  
Cornelia De Lange Syndrome ◽  
Published Data ◽  
Pathogenic Variants ◽  
Diagnostic Center ◽  
High Prevalence ◽  
Strong Source ◽  
Cornelia De Lange

AbstractPostzygotic mosaicism (PZM) in NIPBL is a strong source of causality for Cornelia de Lange syndrome (CdLS) that can have major clinical implications. Here, we further delineate the role of somatic mosaicism in CdLS by describing a series of 11 unreported patients with mosaic disease-causing variants in NIPBL and performing a retrospective cohort study from a Spanish CdLS diagnostic center. By reviewing the literature and combining our findings with previously published data, we demonstrate a negative selection against somatic deleterious NIPBL variants in blood. Furthermore, the analysis of all reported cases indicates an unusual high prevalence of mosaicism in CdLS, occurring in 13.1% of patients with a positive molecular diagnosis. It is worth noting that most of the affected individuals with mosaicism have a clinical phenotype at least as severe as those with constitutive pathogenic variants. However, the type of genetic change does not vary between germline and somatic events and, even in the presence of mosaicism, missense substitutions are located preferentially within the HEAT repeat domain of NIPBL. In conclusion, the high prevalence of mosaicism in CdLS as well as the disparity in tissue distribution provide a novel orientation for the clinical management and genetic counselling of families.

scholarly journals A Broader Perspective on the Prenatal Diagnosis of Cornelia de Lange Syndrome: Review of the Literature and Case Presentation

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 142
Author(s):  
Anca Maria Panaitescu ◽  
Simona Duta ◽  
Nicolae Gica ◽  
Radu Botezatu ◽  
Florina Nedelea ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Cornelia De Lange Syndrome ◽  
Facial Features ◽  
Genetic Condition ◽  
Case Presentation ◽  
Pathogenic Variants ◽  
Limb Reduction ◽  
Ultrasound Findings ◽  
Prenatal Management ◽  
Cornelia De Lange

Cornelia de Lange syndrome (CDLS) is caused by pathogenic variants in genes which are structural or regulatory components of the cohesin complex. The classical Cornelia de Lange (CDLS) phenotype is characterized by distinctive facial features, growth retardation, upper limb reduction defects, hirsutism, and developmental delay. Non-classical phenotypes make this condition heterogeneous. Although CDLS is a heterogeneous clinical and genetic condition, clear diagnostic criteria have been described by specialist consensus. Many of these criteria refer to features that can be seen on prenatal ultrasound. The aim of this paper is twofold: to present the ultrasound findings in fetuses affected by CDLS syndrome; to discuss the recent advances and the limitations in the ultrasound and genetic prenatal diagnosis of CDLS. Our review aims to offer, apart from the data needed to understand the genetics and the prenatal presentation of the disease, a joint perspective of the two specialists involved in the prenatal management of this pathology: the fetal medicine specialist and the geneticist. To better illustrate the data presented, we also include a representative clinical case.

Somatic mosaicism in a Cornelia de Lange syndrome patient withNIPBLmutation identified by different next generation sequencing approaches

2014 ◽  
Vol 86 (6) ◽  
pp. 595-597 ◽  
Author(s):  
C. Baquero-Montoya ◽  
M.C. Gil-Rodríguez ◽  
D. Braunholz ◽  
M.E. Teresa-Rodrigo ◽  
C. Obieglo ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Somatic Mosaicism ◽  
Cornelia De Lange Syndrome ◽  
Syndrome Patient ◽  
Next Generation ◽  
Cornelia De Lange ◽  
Generation Sequencing

scholarly journals Pathogenic variants in EP300 and ANKRD11 in patients with phenotypes overlapping Cornelia de Lange syndrome

2020 ◽  
Vol 182 (7) ◽  
pp. 1690-1696 ◽  
Author(s):  
Francesco Cucco ◽  
Patrizia Sarogni ◽  
Sara Rossato ◽  
Mirella Alpa ◽  
Alessandra Patimo ◽  
...  
Keyword(s):  
Cornelia De Lange Syndrome ◽  
Pathogenic Variants ◽  
Cornelia De Lange

Somatic mosaicism in Cornelia de Lange syndrome: a further contributor to the wide clinical expressivity?

2010 ◽  
Vol 78 (6) ◽  
pp. 560-564 ◽  
Author(s):  
P Castronovo ◽  
A Delahaye-Duriez ◽  
C Gervasini ◽  
J Azzollini ◽  
F Minier ◽  
...  
Keyword(s):  
Somatic Mosaicism ◽  
Cornelia De Lange Syndrome ◽  
Cornelia De Lange

scholarly journals i-gel: a new supraglottic device for effective resuscitation of a very low birthweight infant with Cornelia de Lange syndrome

2015 ◽  
Vol 2015 (mar24 2) ◽  
pp. bcr2014209124-bcr2014209124 ◽  
Author(s):  
A. Galderisi ◽  
G. De Bernardo ◽  
E. Lorenzon ◽  
D. Trevisanuto
Keyword(s):  
Low Birthweight ◽  
Cornelia De Lange Syndrome ◽  
Very Low Birthweight ◽  
Cornelia De Lange ◽  
Very Low Birthweight Infant

scholarly journals Unsuspected somatic mosaicism for FBN1 gene contributes to Marfan syndrome

2021 ◽  
Author(s):  
Pauline Arnaud ◽  
Hélène Morel ◽  
Olivier Milleron ◽  
Laurent Gouya ◽  
Christine Francannet ◽  
...  
Keyword(s):  
Marfan Syndrome ◽  
Somatic Mosaicism ◽  
Variant Calling ◽  
Copy Number Variations ◽  
Pathogenic Variant ◽  
Single Nucleotide Variants ◽  
Bioinformatics Analyses ◽  
Single Nucleotide ◽  
Fbn1 Gene ◽  
Pathogenic Variants

Abstract Purpose Individuals with mosaic pathogenic variants in the FBN1 gene are mainly described in the course of familial screening. In the literature, almost all these mosaic individuals are asymptomatic. In this study, we report the experience of our team on more than 5,000 Marfan syndrome (MFS) probands. Methods Next-generation sequencing (NGS) capture technology allowed us to identify five cases of MFS probands who harbored a mosaic pathogenic variant in the FBN1 gene. Results These five sporadic mosaic probands displayed classical features usually seen in Marfan syndrome. Combined with the results of the literature, these rare findings concerned both single-nucleotide variants and copy-number variations. Conclusion This underestimated finding should not be overlooked in the molecular diagnosis of MFS patients and warrants an adaptation of the parameters used in bioinformatics analyses. The five present cases of symptomatic MFS probands harboring a mosaic FBN1 pathogenic variant reinforce the fact that apparently asymptomatic mosaic parents should have a complete clinical examination and a regular cardiovascular follow-up. We advise that individuals with a typical MFS for whom no single-nucleotide pathogenic variant or exon deletion/duplication was identified should be tested by NGS capture panel with an adapted variant calling analysis.

scholarly journals Targeted Gene Sequencing, Bone Health, and Body Composition in Cornelia de Lange Syndrome

2021 ◽  
Vol 11 (2) ◽  
pp. 710
Author(s):  
Ángel Matute-Llorente ◽  
Ángela Ascaso ◽  
Ana Latorre-Pellicer ◽  
Beatriz Puisac ◽  
Laura Trujillano ◽  
...  
Keyword(s):  
Body Composition ◽  
Lean Mass ◽  
Bone Health ◽  
Cornelia De Lange Syndrome ◽  
Areal Bone Mineral Density ◽  
Childhood And Adolescence ◽  
Mineral Density ◽  
Calcium Phosphorus ◽  
Cornelia De Lange ◽  
Targeted Gene Sequencing

The aim of this study was to evaluate bone health and body composition by dual-energy X-ray absorptiometry (DXA) in individuals with Cornelia de Lange Syndrome (CdLS). Overall, nine individuals with CdLS (five females, all Caucasian, aged 5–38 years) were assessed. Total body less head (TBLH) and lumbar spine (LS) scans were performed, and bone serum biomarkers were determined. Molecular analyses were carried out and clinical scores and skeletal features were assessed. Based on deep sequencing of a custom target gene panel, it was discovered that eight of the nine CdLS patients had potentially causative genetic variants in NIPBL. Fat and lean mass indices (FMI and LMI) were 3.4–11.1 and 8.4–17.0 kg/m2, respectively. For TBLH areal bone mineral density (aBMD), after adjusting for height for age Z-score of children and adolescents, two individuals (an adolescent and an adult) had low BMD (aBMD Z-scores less than –2.0 SD). Calcium, phosphorus, 25-OH-vitamin D, parathyroid hormone, and alkaline phosphatase levels were 2.08–2.49 nmol/L, 2.10–3.75 nmol/L, 39.94–78.37 nmol/L, 23.4–80.3 pg/mL, and 43–203 IU/L, respectively. Individuals with CdLS might have normal adiposity and low levels of lean mass measured with DXA. Bone health in this population seems to be less of a concern during childhood and adolescence. However, they might be at risk for impaired bone health due to low aBMD in adulthood.

The Cornelia de Lange syndrome

1963 ◽  
Vol 63 (5) ◽  
pp. 1000-1020 ◽  
Author(s):  
Louis J. Ptacek ◽  
John M. Opitz ◽  
David W. Smith ◽  
Theo Gerritsen ◽  
Harry A. Waisman
Keyword(s):  
Cornelia De Lange Syndrome ◽  
Cornelia De Lange
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