Atypical copy number abnormalities in 22q11.2 region: Report of three cases

Molck, Miriam Coelho; Vieira, Társis Paiva; Sgardioli, Ilária Cristina; Simioni, Milena; Santos, Ana Paula dos; Souza, Josiane; Monteiro, Fabíola Paoli

doi:10.1016/j.ejmg.2013.07.002

Cited by 18 publications

(19 citation statements)

References 62 publications

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“…This microdeletion could not be identified by FISH with the probe commonly used for the proximal 22q11.2 region, confirming that MLPA is quite effective in detecting atypical deletions involving smaller and variable regions within the 22q11.2 region [Fernández et al, 2005;Jalali et al, 2008;Molck et al, 2013].…”

Section: Discussionmentioning

confidence: 85%

“…Targeted approaches, such as FISH, real-time PCR, analysis of polymorphic DNA markers, and quantitative fluorescent PCR, though well established and fast, are only effective in detecting common deletions [Fernán-dez et al, 2005;Oh et al, 2007;Molck et al, 2013;Vieira et al, 2013;Poirsier et al, 2016]. Thus, negative results may lead to false negative diagnosis, since atypical 22q11.2 deletions may occur [Beaujard et al, 2009;Molck et al, 2013].…”

Section: Discussionmentioning

confidence: 99%

“…In this context, MLPA is a more effective technique for the diagnosis of 22q11.2DS, and identifying typical/atypical deletions, these in smaller size and/or variable regions within the 22q11.2 region [Vorstman et al, 2006;Molck et al, 2013Molck et al, , 2015. MLPA detected 4 deletions of 3 Mb and 1 atypical distal deletion that would not have been detected by FISH.…”

Section: Discussionmentioning

confidence: 99%

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Diagnostic Approach to Microdeletion Syndromes Based on 22q11.2 Investigation: Challenges in Four Cases

et al. 2017

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In the last few decades, different methods for the detection of genomic imbalances, such as the microdeletion syndromes, were developed. The 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion syndrome and presents wide clinical heterogeneity. The aim of this study was to describe 4 unusual cases of genomic imbalances found in individuals with suspected microdeletion syndromes. Different methods were necessary to complete the diagnosis and to obtain information for genetic counseling. The study was retrospective and descriptive. From August 2014 to December 2015, 39 individuals were assessed using FISH and/or MLPA; in 15 cases, chromosomal microarray (CMA) analysis was carried out. Of 39 registered individuals, we found deletions in the 22q11.2 region in 10 individuals (8 individuals with 22q11.2DS and 2 individuals presenting with atypical deletions in the 22q11.2 region: 1 distal deletion and 1 central deletion). In one case with a typical 22q11.2 deletion, a familial balanced translocation was detected. In another case without a 22q11.2 deletion, a 6p duplication concomitant with a 9p deletion was detected by CMA. Clinical data are reported and diagnostic investigations are discussed. Essential aspects for the understanding of different diagnostic techniques of genomic imbalances are considered, and the 4 cases described underline the complexity and the difficulties involved in the diagnostic process. The approach is informative for clinical practice and may be applied in other contexts of genomic imbalance investigation in microdeletion syndromes.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Diagnostic Approach to Microdeletion Syndromes Based on 22q11.2 Investigation: Challenges in Four Cases

et al. 2017

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“…c Data from Rauch et al, 1999Rauch et al, , 2005Saitta et al, 1999;Mikhail et al, 2007Mikhail et al, , 2014Ben-Shachar et al, 2008;Jalali et al, 2008;Rødningen et al, 2008;Xu et al, 2008;Ogilvie et al, 2009;Bruce et al, 2010;Madan et al, 2010;Garavelli et al, 2011;Tan et al, 2011;Verhoeven et al, 2011;Yu et al, 2011;Breckpot et al, 2012;Fagerberg et al, 2013;Molck et al, 2013;Rump et al, 2014. d Data from Shaikh et al, 2000;Rauch et al, 2005;Nik-Zainal et al, 2011;Yu et al, 2011;Mikhail et al, 2014. e Data from Wieser et al, 2005;Jackson et al, 2007;Lafay-Cousin et al, 2009;Beddow et al, 2011;Bourdeaut et al, 2011;Tan et al, 2011;Toth et al, 2011. f Index cases and familial carriers.…”

Section: Central Deletions (B-d C-d)mentioning

confidence: 99%

“…The reported deletions have largely been de novo and fetuses/neonates having distal type I deletions tended to require pregnancy and delivery management that individuals with the other types of deletions typically do not ( table 3 ). A total of 45 individuals have been reported with distal type I deletions, including an atypical B-F deletion observed by Molck et al [2013] [ Rauch et al, 1999Rauch et al, , 2005Saitta et al, 1999;Mikhail et al, 2007Mikhail et al, , 2014Ben-Shachar et al, 2008;Jalali et al, 2008;Rødningen et al, 2008;Xu et al, 2008;Ogilvie et al, 2009;Bruce et al, 2010;Madan et al, 2010;Garavelli et al, 2011;Tan et al, 2011;Verhoeven et al, 2011;Yu et al, 2011;Breckpot et al, 2012;Fagerberg et al, 2013;Molck et al, 2013;Rump et al, 2014]. The individuals reported in Ravnan et al [2006] Cardiac defects were observed in 24/45 (53%) and were primarily septal defects.…”

Section: Type I (C-e D-e D-f)mentioning

confidence: 99%

22q11.21 Deletion Syndromes: A Review of Proximal, Central, and Distal Deletions and Their Associated Features

Burnside

2015

Cytogenet Genome Res

1,436

149

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Chromosome 22q11.21 contains a cluster of low-copy repeats (LCRs), referred to as LCR22A-H, that mediate meiotic non-allelic homologous recombination, resulting in either deletion or duplication of various intervals in the region. The deletion of the DiGeorge/velocardiofacial syndrome interval LCR22A-D is the most common recurrent microdeletion in humans, with an estimated incidence of ∼1:4,000 births. Deletion of other intervals in 22q11.21 have also been described, but the literature is often confusing, as the terms ‘proximal', ‘nested', ‘distal', and ‘atypical' have all been used to describe various of the other intervals. Individuals with deletions tend to have features with widely variable expressivity, even among families. This review concisely delineates each interval and classifies the reported literature accordingly.

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Are 22q11.2 distal deletions associated with math difficulties?

Carvalho

Vianna

Oliveira

et al. 2014

American J of Med Genetics Pt A

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Approximately 6% of school-aged children have math difficulties (MD). A neurogenetic etiology has been suggested due to the presence of MD in some genetic syndromes such as 22q11.2DS. However, the contribution of 22q11.2DS to the MD phenotype has not yet been investigated. This is the first population-based study measuring the frequency of 22q11.2DS among school children with MD. Children (1,564) were identified in the schools through a screening test for language and math. Of these children, 152 (82 with MD and 70 controls) were selected for intelligence, general neuropsychological, and math cognitive assessments and for 22q11.2 microdeletion screening using MLPA. One child in the MD group had a 22q11.2 deletion spanning the LCR22-4 to LCR22-5 interval. This child was an 11-year-old girl with subtle anomalies, normal intelligence, MD attributable to number sense deficit, and difficulties in social interactions. Only 19 patients have been reported with this deletion. Upon reviewing these reports, we were able to characterize a new syndrome, 22q11.2 DS (LCR22-4 to LCR22-5), characterized by prematurity; pre- and postnatal growth restriction; apparent hypotelorism, short/upslanting palpebral fissures; hypoplastic nasal alae; pointed chin and nose; posteriorly rotated ears; congenital heart defects; skeletal abnormalities; developmental delay, particularly compromising the speech; learning disability (including MD, in one child); intellectual disability; and behavioral problems. These results suggest that 22q11.2 DS (LCR22-4 to LCR22-5) may be one of the genetic causes of MD.

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Atypical copy number abnormalities in 22q11.2 region: Report of three cases

Cited by 18 publications

References 62 publications

Diagnostic Approach to Microdeletion Syndromes Based on 22q11.2 Investigation: Challenges in Four Cases

Diagnostic Approach to Microdeletion Syndromes Based on 22q11.2 Investigation: Challenges in Four Cases

22q11.21 Deletion Syndromes: A Review of Proximal, Central, and Distal Deletions and Their Associated Features

Are 22q11.2 distal deletions associated with math difficulties?

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