Contribution of SNP arrays in diagnosis of deletion 2p11.2–p12

Rocca, Maria Santa; Fabretto, Antonella; Faletra, Flavio; Carlet, Ombretta; Skabar, Aldo; Gasparini, Paolo; Pecile, Vanna

doi:10.1016/j.gene.2011.10.035

Cited by 6 publications

(10 citation statements)

References 22 publications

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“…A very similar deletion was reported recently, 9 which has an identical proximal breakpoint (Figure 2). The distal breakpoints differ by a mere 5 kbp, which is within experimental variation of the array.…”

Section: Discussionsupporting

confidence: 82%

“…MIM 613564). [9][10][11][12] All show mild-to-moderate intellectual disability, a very happy disposition, speech delay, delayed motor development and minor facial anomalies such as high forehead, broad nasal bridge and large low set ears (Table 1). Despite the very large size of the del(2)(p11.2p12), the clinical phenotype is relatively mild when compared generally with similar-sized deletions reported in literature.…”

Section: Discussionmentioning

confidence: 99%

“…21 Recurrent deletion 2p11.2-2p12 is exceedingly rare, given the very limited literature on this aberration to date. 9 Its scarcity may be related to the very large intervening segment that is flanked by the LCRs (Figure 2) as the physical proximity of LCRs may be positively related to the chance of non-allelic synapsis in meiosis. 22,23 The percentage identity of the two misaligning LCRs determines NAHR chance and for the 2p11.2 and 2p12 breakpoint-flanking LCRs this is extremely high (499% identity).…”

Section: Recurrent 2p112-2p12 Deletion Syndrome Sjc Stevens Et Almentioning

confidence: 99%

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A recurrent deletion syndrome at chromosome bands 2p11.2-2p12 flanked by segmental duplications at the breakpoints and including REEP1

et al. 2014

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We identified an identical and recurrent 9.4-Mbp deletion at chromosome bands 2p11.2-2p12, which occurred de novo in two unrelated patients. It is flanked at the distal and proximal breakpoints by two homologous segmental duplications consisting of low copy repeat (LCR) blocks in direct orientation, which have 499% sequence identity. Despite the fact that the deletion was almost 10 Mbp in size, the patients showed a relatively mild clinical phenotype, that is, mild-to-moderate intellectual disability, a happy disposition, speech delay and delayed motor development. Their phenotype matches with that of previously described patients. The 2p11.2-2p12 deletion includes the REEP1 gene that is associated with spastic paraplegia and phenotypic features related to this are apparent in most 2p11.2-2p12 deletion patients, but not in all. Other hemizygous genes that may contribute to the clinical phenotype include LRRTM1 and CTNNA2. We propose a recurrent but rare 2p11.2-2p12 deletion syndrome based on (1) the identical, non-random localisation of the de novo deletion breakpoints in two unrelated patients and a patient from literature, (2) the patients' phenotypic similarity and their phenotypic overlap with other 2p deletions and (3) the presence of highly identical LCR blocks flanking both breakpoints, consistent with a non-allelic homologous recombination (NAHR)-mediated rearrangement.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Recurrent 2p112-2p12 Deletion Syndrome Sjc Stevens Et Almentioning

confidence: 99%

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A recurrent deletion syndrome at chromosome bands 2p11.2-2p12 flanked by segmental duplications at the breakpoints and including REEP1

et al. 2014

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“…The CNV in the 2p12 region (477, Table ) resulted in a simultaneous deletion of intron 7 of the CTNNA2 and the LRRTM1 gene, with LRRTM1 haploinsufficiency implicated in schizophrenia and autism . We are reporting the smallest possible causal deletion resulting in typical autism without dysmorphic features despite the additional VOUS (20p12.1 duplication), possibly not contributing to the phenotype.…”

Section: Discussionmentioning

confidence: 91%

Recurrent copy number variations as risk factors for autism spectrum disorders: analysis of the clinical implications

et al. 2016

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Chromosomal microarray analysis (CMA) is currently considered a first-tier diagnostic assay for the investigation of autism spectrum disorders (ASD), developmental delay and intellectual disability of unknown etiology. High-resolution arrays were utilized for the identification of copy number variations (CNVs) in 195 ASD patients of Greek origin (126 males, 69 females). CMA resulted in the detection of 65 CNVs, excluding the known polymorphic copy number polymorphisms also found in the Database of Genomic Variants, for 51/195 patients (26.1%). Parental DNA testing in 20/51 patients revealed that 17 CNVs were de novo, 6 paternal and 3 of maternal origin. The majority of the 65 CNVs were deletions (66.1%), of which 5 on the X-chromosome while the duplications, of which 7 on the X-chromosome, were rarer (22/65, 33.8%). Fifty-one CNVs from a total of 65, reported for our cohort of ASD patients, were of diagnostic significance and well described in the literature while 14 CNVs (8 losses, 6 gains) were characterized as variants of unknown significance and need further investigation. Among the 51 patients, 39 carried one CNV, 10 carried two CNVs and 2 carried three CNVs. The use of CMA, its clinical validity and utility was assessed.

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“…So far, few cases have been reported with deletions larger than 7.5 MB with the minimally commonly deleted region including three candidate genes, CTNNA2, LRRTM1 and REEP1, highly expressed in brain. [1][2][3][4][5] Patients with these microdeletions show intellectual disability, growth retardation, speech delay, minor facial anomalies (high forehead, frontal bossing, broad nasal bridge, abnormal ears) and congenital defects.…”

Section: Introductionmentioning

confidence: 99%

An intragenic deletion within CTNNA2 intron 7 in a boy with short stature and speech delay: A case report

Paganelli

Giordano

Meazza

et al. 2017

SAGE Open Medical Case Reports

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Background/Objectives:Deletions on the short arm of chromosome 2 at bands p11 and p12 have been detected in association with short stature, mild mental retardation and speech delay.Results:We describe a 4 year-old boy with some facial dysmorphic traits, congenital malformations and pre- and post-natal growth failure. He also presented marked expressive language problems. The molecular karyotype revealed a 108 Kb deletion within the seventh intron of the CTNNA2 gene at 2p11.2-p12. We observed that some features (short stature, facial dysmorphisms and speech delay) were present in our patient and in patients carrying much larger overlapping deletions.Conclusions:The description of this small intragenic rearrangement might help to elucidate the role of the single genes included in the 2p11.2-p12 critical region.

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Contribution of SNP arrays in diagnosis of deletion 2p11.2–p12

Cited by 6 publications

References 22 publications

A recurrent deletion syndrome at chromosome bands 2p11.2-2p12 flanked by segmental duplications at the breakpoints and including REEP1

A recurrent deletion syndrome at chromosome bands 2p11.2-2p12 flanked by segmental duplications at the breakpoints and including REEP1

Recurrent copy number variations as risk factors for autism spectrum disorders: analysis of the clinical implications

An intragenic deletion within CTNNA2 intron 7 in a boy with short stature and speech delay: A case report

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