Germline mosaicism in Cornelia de Lange syndrome

Slavin, Thomas P.; Lazebnik, Noam; Clark, Dinah; Vengoechea, Jaime; Cohen, Leslie; Kaur, Maninder; Konczal, Laura; Crowe, Carol A.; Corteville, Jane E.; Nowaczyk, Małgorzata J.M.; Byrne, Janice L. B.; Jackson, Laird G.; Krantz, Ian D.

doi:10.1002/ajmg.a.35381

Cited by 36 publications

(43 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A de novo chromosome abnormality t(5;13)(p13.1;q12.1) truncating NIPBL is detected in a single patient, 3 gross deletions are detected in 3 different families, and 23 different gross deletions are identified in 23 families . In one of the families three siblings, but not the parents, had a deletion, suggesting germline mosaicism .…”

Section: The Genetic Basis Of Cdlsmentioning

confidence: 95%

Cornelia de Lange syndrome

et al. 2014

View full text Add to dashboard Cite

Cornelia de Lange syndrome (CdLS; MIM #122470, 300590, 610759, 614701, 300882) is a rare and clinically variable disorder that affects multiple organs. It is characterized by intellectual disability (mild to severe), distinctive facial features, prenatal and postnatal growth retardation, and hirsutism. Congenital anomalies include malformations of the upper limbs, gastrointestinal malformation/rotation, pyloric stenosis, diaphragmatic hernia, heart defects and genitourinary malformations. Gastroesophageal reflux disease is present in almost all patients. In addition to classic forms, milder phenotypes have been reported. To date five genes [NIPBL (Nipped-B-like protein), SMC1A (structural maintenance of chromosomes 1A), SMC3 (structural maintenance of chromosomes 3), RAD21 (human homolog of Schizosaccharomyces pombe radiation sensitive mutant 21) and HDAC8 (histone deacetylase 8)] have been associated with CdLS and mutations of these genes comprise the underlying defect in 70% of the patients. Here, we will provide a brief review of the clinical features of CdLS, summarize the known underlying genetic defects, prenatal and postnatal diagnosis possibilities, and genetic counseling.

show abstract

Section: The Genetic Basis Of Cdlsmentioning

confidence: 95%

Cornelia de Lange syndrome

et al. 2014

View full text Add to dashboard Cite

show abstract

“…The exact recurrence risk for unaffected parents is classically quoted as 1.5% because of germline mosaicism. Recently higher figures (up to 5%) have been proposed and the exact recurrence is still unknown (Table ) …”

Section: Other Genetic Syndromes Associated With Cardiac Anomaliesmentioning

confidence: 99%

Fetal cardiac abnormalities: Genetic etiologies to be considered

et al. 2019

View full text Add to dashboard Cite

Congenital heart diseases are a common prenatal finding. The prenatal identification of an associated genetic syndrome or a major extracardiac anomaly helps to understand the etiopathogenic diagnosis. Besides, it also assesses the prognosis, management, and familial recurrence risk while strongly influences parental decision to choose termination of pregnancy or postnatal care. This review article describes the most common genetic diagnoses associated with a prenatal finding of a congenital heart disease and a suggested diagnostic process.

show abstract

“…Most of these cases are possibly owing to mosaicism, which in some individuals can be difficult to discern. 20 It is also hypothesized that other yet unknown gene/s is/are likely involved as well. Moreover, there are individuals with atypical CdLS phenotypes that phenotypically overlap with the classic CdLS phenotype and who are considered to have a 'cohesinopathy'.…”

Section: Mutational Spectrummentioning

confidence: 99%