Copy number variation analysis of patients with intellectual disability from North-West Spain

Quintela, Inés; Eirís-Puñal, Jesús; Gómez-Lado, Carmen; Pérez-Gay, Laura; Dacruz, David; Cruz, Raquel; Castro-Gago, Manuel; Míguez, L.; Carracedo, Ángel; Barros, Francisco

doi:10.1016/j.gene.2017.05.032

Cited by 21 publications

(41 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Such solid agreement for pCNV frequency correlates also to a more precise and internationally defined criteria for pCNV classification. The pCNV DR indicated by our study is 11%, in line with the lower limit of the interval extrapolated from different studies in the literature (10%–16%) (Ahn et al, ; Bartnik et al, , ; Battaglia et al, ; Cappuccio et al, ; Carreira et al, ; D'Arrigo et al, ; Fry et al, ; Kaminsky et al, ; Mc Cormack et al, ; Quintela et al, ; Vianna et al, ; Wincent et al, ).…”

Section: Discussionsupporting

confidence: 89%

“…In addition to non‐syndromic CM, also non‐syndromic neurodevelopmental disorders were considered as negative markers, as also confirmed in the subgroups of patients exclusively referred for non‐syndromic ID/DD, ASD, or LD. The literature reports other cohorts of patients referred for ID/DD, but such cohorts included both non‐syndromic and syndromic ID/DD making a comparison with our study not appropriate (Bartnik et al, ; D'Arrigo et al, ; Di Gregorio et al, ; Quintela et al, ). ID/DD combined to any other single clinical sign and non‐syndromic D emerged neither as a negative nor as a positive clinical marker.…”

Section: Discussionmentioning

confidence: 94%

See 1 more Smart Citation

Testing single/combined clinical categories on 5110 Italian patients with developmental phenotypes to improve array‐based detection rate

Catusi

Recalcati

Bestetti

et al. 2019

Molec Gen & Gen Med

View full text Add to dashboard Cite

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractBackground: Chromosomal microarray analysis (CMA) is nowadays widely used in the diagnostic path of patients with clinical phenotypes. However, there is no ascertained evidence to date on how to assemble single/combined clinical categories of developmental phenotypic findings to improve the array-based detection rate. Methods: The Italian Society of Human Genetics coordinated a retrospective study which included CMA results of 5,110 Italian patients referred to 17 genetics laboratories for variable combined clinical phenotypes. Results: Non-polymorphic copy number variants (CNVs) were identified in 1512 patients (30%) and 615 (32%) present in 552 patients (11%) were classified as pathogenic. CNVs were analysed according to type, size, inheritance pattern, distribution among chromosomes, and association to known syndromes. In addition, the evaluation of the detection rate of clinical subgroups of patients allowed to associate dysmorphisms and/or congenital malformations combined with any other single clinical sign to an increased detection rate, whereas non-syndromic neurodevelopmental signs and non-syndromic congenital malformations to a decreased detection rate. Conclusions: Our retrospective study resulted in confirming the high detection rate of CMA and indicated new clinical markers useful to optimize their inclusion in the diagnostic and rehabilitative path of patients with developmental phenotypes. K E Y W O R D SChromosomal microarray analysis (CMA), clinical marker identification, detection rate, pathogenic

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 94%

Testing single/combined clinical categories on 5110 Italian patients with developmental phenotypes to improve array‐based detection rate

Catusi

Recalcati

Bestetti

et al. 2019

Molec Gen & Gen Med

View full text Add to dashboard Cite

show abstract

“…Outside of Kleefstra syndrome, de novo deletions of GLP have been detected in severe intellectual disability Copy Number Variant (CNV studies) [35][36][37], and GLP associated chromatin Figure 1. Maintenance of DNA methylation: Glp and G9a are known to target H3K9 for mono and di-methylation, they have also recently been found to methylate the H3K9 mimic on DNA ligase 1 (LIG1).…”

Section: Intellectual Disabilitymentioning

confidence: 99%

“…Outside of Kleefstra syndrome, de novo deletions of GLP have been detected in severe intellectual disability Copy Number Variant (CNV studies) [35][36][37], and GLP associated chromatin regulators have also been linked to sporadic intellectual disability in chromosomal microarray [37]. Furthermore, exome studies of patients with intellectual disability again link GLP to a wider epigenetic regulatory network important to cognitive function [31,38].…”

Section: Intellectual Disabilitymentioning

confidence: 99%

EHMT1/GLP; Biochemical Function and Association with Brain Disorders

Adam

Isles

2017

Epigenomes

View full text Add to dashboard Cite

Abstract:The gene EHMT1 that encodes the Euchromatic Histone Methyltransferase-1, also known as GLP (G9a-like protein), has been associated with a number of neurodevelopmental and neurodegenerative disorders. GLP is a member of the euchromatic lysine histone methyltransferase family, along with EHMT2 or G9A. As its name implies, Ehmt1/GLP is involved in the addition of methyl groups to histone H3 lysine 9, a generally repressive mark linked to classical epigenetic process such as genomic imprinting, X-inactivation, and heterochromatin formation. However, GLP also plays both a direct and indirect role in regulating DNA-methylation. Here, we discuss what is currently known about the biochemical function of Ehmt1/GLP and its association, via various genetic studies, with brain disorders.

show abstract

“…Despite the presence of CNVs in healthy individuals, they have also been associated with changes in gene expression, alterations in gene dosage, and a wide range of other outcomes, including the onset of disease (Redon et al, 2006;Zarrei et al, 2015). For example, pathogenic CNVs have been associated with congenital malformations (Di Gregorio et al, 2015), schizophrenia (Marshall et al, 2017), and environmental exposures (Du et al, 2017;Martinez et al, 2010), among others (Cuccaro, De Marco, Cittadella, & Cavallaro, 2017;Poniah et al, 2017;Quintela et al, 2017). Thus, the ability to identify and characterize CNVs as pathogenic or benign may provide novel insight into a variety of adverse health outcomes.…”

Section: Introductionmentioning

confidence: 99%

Critical evaluation of copy number variant calling methods using DNA methylation

Kilaru

Knight

Katrinli

et al. 2019

Genetic Epidemiology

View full text Add to dashboard Cite

Recent technological and methodological developments have enabled the use of array‐based DNA methylation data to call copy number variants (CNVs). ChAMP, Conumee, and cnAnalysis450k are popular methods currently used to call CNVs using methylation data. However, so far, no studies have analyzed the reliability of these methods using real samples. Data from a cohort of individuals with genotype and DNA methylation data generated using the HumanMethylation450 and MethylationEPIC BeadChips were used to assess the consistency between the CNV calls generated by methylation and genotype data. We also took advantage of repeated measures of methylation data collected from the same individuals to compare the reliability of CNVs called by ChAMP, Conumee, and cnAnalysis450k for both the methylation arrays. ChAMP identified more CNVs than Conumee and cnAnalysis450k for both the arrays and, as a consequence, had a higher overlap (~62%) with the calls from the genotype data. However, all methods had relatively low reliability. For the MethylationEPIC array, Conumee had the highest reliability (57.6%), whereas for the HumanMethylation450 array, cnAnalysis450k had the highest reliability (43.0%). Overall, the MethylationEPIC array provided significant gains in reliability for CNV calling over the HumanMethylation450 array but not for overlap with CNVs called using genotype data.

show abstract

Copy number variation analysis of patients with intellectual disability from North-West Spain

Cited by 21 publications

References 90 publications

Testing single/combined clinical categories on 5110 Italian patients with developmental phenotypes to improve array‐based detection rate

Testing single/combined clinical categories on 5110 Italian patients with developmental phenotypes to improve array‐based detection rate

EHMT1/GLP; Biochemical Function and Association with Brain Disorders

Critical evaluation of copy number variant calling methods using DNA methylation

Contact Info

Product

Resources

About