Table 1. [Molecular Genetic Testing Used in Cornelia de Lange Syndrome]. - GeneReviews® - NCBI Bookshelf

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Table 1.

Molecular Genetic Testing Used in Cornelia de Lange Syndrome

Gene ^1, 2	Proportion of CdLS Attributed to Pathogenic Variants in Gene	Proportion of Probands with a Pathogenic Variant ³ Detectable by Method
Gene ^1, 2		Sequence analysis ⁴	Gene-targeted deletion/duplication analysis ⁵
BRD4	<1%	3/4 ⁶	1/4 ⁶
HDAC8	~4%	~90% ⁷	~10% ⁷
NIPBL	~80% ^8, 9	~97% ⁹	~3% ^10, 11
RAD21	<1% ¹²	20/22 ¹²	2/22 ¹²
SMC1A	~5% ¹³	~100%
SMC3	1%-2% ¹⁴	~97%	~3%
Unknown	3%-5%

1.: Genes are listed in alphabetic order.
2.: See Table A. Genes and Databases for chromosome locus and protein.
3.: See Molecular Genetics for information on allelic variants detected in these genes.
4.: Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
5.: Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. Gene-targeted deletion/duplication testing will detect deletions ranging from a single exon to the whole gene; however, breakpoints of large deletions and/or deletion of adjacent genes (e.g., those described by Olley et al [2018]) may not be detected by these methods.
6.: Olley et al [2018]
7.: Ansari et al [2014], Kaiser et al [2014]
8.: Borck et al [2004], Gillis et al [2004], Tonkin et al [2004], Bhuiyan et al [2006], Musio et al [2006], Yan et al [2006], Selicorni et al [2007], Huisman et al [2013]
9.: Somatic mosaicism for NIPBL has been reported in approximately 10%-15% of individuals. Obtaining a buccal sample at the time of collecting a peripheral blood sample can be considered [Huisman et al 2013]. Screening for NIPBL mosaicism can be pursued if CdLS is strongly suspected and molecular genetic testing on a peripheral blood sample is normal.
10.: Gene-targeted deletion/duplication analysis of NIPBL detects ~3% of NIPBL-CdLS [Pehlivan et al 2012, Russo et al 2012, Ansari et al 2014].
11.: Cytogenetic testing or chromosomal microarray (CMA) may also be considered in those with classic features of CdLS but normal molecular genetic testing because a few individuals with large deletions of 5p13 that include NIPBL have been reported [Taylor & Josifek 1981, Hulinsky et al 2005, Hayashi et al 2007].
12.: Deardorff et al [2012], Krab et al [2020]
13.: Musio et al [2006], Borck et al [2007], Deardorff et al [2007], Huisman et al [2017]
14.: Gil-Rodríguez et al [2015]

From: Cornelia de Lange Syndrome

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