Differing Microdeletion Sizes and Breakpoints in Chromosome 7q11.23 in Williams-Beuren Syndrome Detected by Chromosomal Microarray Analysis

Li, Lin; Huang, Liwu; Luo, Yang; Huang, Xuan; Lin, Shaobin; Fang, Qun

doi:10.1159/000443942

Cited by 18 publications

(11 citation statements)

References 24 publications

(22 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The analysis of deletion/duplication is highly relevant for genotype–phenotype correlation, since deletions are generally more significant than duplications as stated in a previous general review [ 2 ]. As the size of a deletion defines the number of affected genes [ 18 ], depending on the resolution of the corresponding platform, the exact sizes of the corresponding CNV can be characterized and define a specific syndrome [ 19 ]. One of the reasons why deletions have more effect than duplications, is because some genes require two copies for its normal expression.…”

Section: Discussionmentioning

confidence: 99%

CGH analysis in Colombian patients: findings of 1374 arrays in a seven-year study

2018

View full text Add to dashboard Cite

BackgroundArray-based comparative genome hybridization (array CGH) is a first-line test used in the genetic evaluation of individuals with multiple anomalies, developmental delays, and cognitive deficits. In this study, we analyzed clinical indications and findings of array CGH tests of Colombian individuals forwarded to a reference laboratory over a period of seven years in order to evaluate the diagnostic performance of the test in our population.ResultsThe results of 1374 array CGH analyses of Colombian individuals were referred to the Andean Reference Institute in Colombia (Instituto de Referencia Andino) during a 7-year period (2009–2015). Chromosomal imbalances were detected in 488 cases (35%), whereas 121 cases were classified as nonpathogenic variants, 65 cases (4.7%) were classified as variants of uncertain significance, and 302 cases (22%) were classified as abnormal or pathogenic. The most common findings in the abnormal and/or pathogenic set were deletions, followed by duplications and complex rearrangements. Variants in the carrier status of autosomal recessive diseases were identified as incidental findings in 29 subjects (2%).ConclusionsClinical indications preceding the referral of aCGH in Colombian patients are not standardized and result in unexpected pathogenic variants as well as secondary findings that need careful interpretation. Development of local infrastructure will probably improve the communication between all stakeholders, to ensure accurate clinical diagnoses.

show abstract

Section: Discussionmentioning

confidence: 99%

CGH analysis in Colombian patients: findings of 1374 arrays in a seven-year study

2018

View full text Add to dashboard Cite

show abstract

“…Although sharing deleted genes, the 21 different microdeletions analyzed do not appear to share common breakpoints, a finding which may account for non recurrent microdeletions at the population level [ 30 , 31 ]. The different rearrangement sizes, genomic extents, and breakpoint positions suggest non-homologous end joining (NHEJ) and replication mechanisms as the main causative drivers of the described microdeletions [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

8p23.2-pter Microdeletions: Seven New Cases Narrowing the Candidate Region and Review of the Literature

Catusi

Garzo

Capra

et al. 2021

Genes

View full text Add to dashboard Cite

To date only five patients with 8p23.2-pter microdeletions manifesting a mild-to-moderate cognitive impairment and/or developmental delay, dysmorphisms and neurobehavioral issues were reported. The smallest microdeletion described by Wu in 2010 suggested a critical region (CR) of 2.1 Mb including several genes, out of which FBXO25, DLGAP2, CLN8, ARHGEF10 and MYOM2 are the main candidates. Here we present seven additional patients with 8p23.2-pter microdeletions, ranging from 71.79 kb to 4.55 Mb. The review of five previously reported and nine Decipher patients confirmed the association of the CR with a variable clinical phenotype characterized by intellectual disability/developmental delay, including language and speech delay and/or motor impairment, behavioral anomalies, autism spectrum disorder, dysmorphisms, microcephaly, fingers/toes anomalies and epilepsy. Genotype analysis allowed to narrow down the 8p23.3 candidate region which includes only DLGAP2, CLN8 and ARHGEF10 genes, accounting for the main signs of the broad clinical phenotype associated to 8p23.2-pter microdeletions. This region is more restricted compared to the previously proposed CR. Overall, our data favor the hypothesis that DLGAP2 is the actual strongest candidate for neurodevelopmental/behavioral phenotypes. Additional patients will be necessary to validate the pathogenic role of DLGAP2 and better define how the two contiguous genes, ARHGEF10 and CLN8, might contribute to the clinical phenotype.

show abstract

“…Incidence at birth is estimated at 1/20,000. WBS is typically caused by a 1.5 Mb deletion at 7q11.23, with recurrent breakpoints within low copy repeats (LCRs) with a high degree of identity localized at the extremities of the single copy critical region (Li et al, 2015). LCRs misalignment rather than homologous recombination during meiosis results in the deletion of the interstitial region.…”

Section: Introductionmentioning

confidence: 99%

Atypical 7q11.23 deletions excluding ELN gene result in Williams–Beuren syndrome craniofacial features and neurocognitive profile

Alesi

Loddo

Orlando

et al. 2020

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Williams–Beurens syndrome (WBS) is a rare genetic disorder caused by a recurrent 7q11.23 microdeletion. Clinical characteristics include typical facial dysmorphisms, weakness of connective tissue, short stature, mild to moderate intellectual disability and distinct behavioral phenotype. Cardiovascular diseases are common due to haploinsufficiency of ELN gene. A few cases of larger or smaller deletions have been reported spanning towards the centromeric or the telomeric regions, most of which included ELN gene. We report on three patients from two unrelated families, presenting with distinctive WBS features, harboring an atypical distal deletion excluding ELN gene. Our study supports a critical role of CLIP2, GTF2IRD1, and GTF2I gene in the WBS neurobehavioral profile and in craniofacial features, highlights a possible role of HIP1 in the autism spectrum disorder, and delineates a subgroup of WBS individuals with an atypical distal deletion not associated to an increased risk of cardiovascular defects.

show abstract

Differing Microdeletion Sizes and Breakpoints in Chromosome 7q11.23 in Williams-Beuren Syndrome Detected by Chromosomal Microarray Analysis

Cited by 18 publications

References 24 publications

CGH analysis in Colombian patients: findings of 1374 arrays in a seven-year study

CGH analysis in Colombian patients: findings of 1374 arrays in a seven-year study

8p23.2-pter Microdeletions: Seven New Cases Narrowing the Candidate Region and Review of the Literature

Atypical 7q11.23 deletions excluding ELN gene result in Williams–Beuren syndrome craniofacial features and neurocognitive profile

Contact Info

Product

Resources

About