Implications of COMT long-range interactions on the phenotypic variability of 22q11.2 deletion syndrome

Zeitz, Μ.; Lerner, Paula P; Ay, Ferhat; Nostrand, Eric L. Van; Heidmann, Julia D.; Noble, William Stafford; Hoffman, Andrew R.

doi:10.4161/nucl.27364

Cited by 17 publications

(16 citation statements)

References 38 publications

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“…Which other factors are necessary to result in abnormal phenotypes in ascertained individuals with these CNVs remains to be determined. It is possible that phenotypic similarity and variability of 22q11.2 CNVs may be impacted by dysregulation of genes via loss of long-range regulatory sequences that could affect either common genes and/or common developmental pathways [Yamagishi and Srivastava, 2003;Zeitz et al, 2013]. Indeed, Zeitz et al [2013] demonstrated long-range chromatin interaction of COMT in the proximal 22q11.2 region with genes on other chromosomes, as well as with MAPK1 in the distal 22q11.2 region, supporting this interpretation.…”

Section: Variability Of Phenotypesupporting

confidence: 69%

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

Burnside

2015

Cytogenet Genome Res

1,443

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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Section: Variability Of Phenotypesupporting

confidence: 69%

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

Burnside

2015

Cytogenet Genome Res

1,443

149

View full text Add to dashboard Cite

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“…CNVs are polymorphic and seen in the DGV database, however the frequency seen within our OAVS When analyzing the pathogenicity of the CNVs, we have identified reports of patients with OAVS features and CNVs within the Cat Eye region [54,55]. Moreover, chromosome 22q has been repeatedly reported in association with OAVS (2,(7)(8).…”

Section: Cnvs On 22q1121mentioning

confidence: 79%

“…In fact, the authors show that chromosomal rearrangements on 22q11 can have widespread effects on chromatin organization, and may contribute to the inherent phenotypic variability associated with those rearrangements [55]. The expression of genes on 22q might be disturbed during development by the presence of genomic imbalances (CNVs), increasing the susceptibility for OAVS craniofacial abnormalities.…”

Section: Accepted Manuscriptmentioning

confidence: 98%

Oculo-auriculo-vertebral spectrum: Clinical and molecular analysis of 51 patients

Beleza-Meireles

Hart

Clayton‐Smith³

et al. 2015

European Journal of Medical Genetics

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“…39 The phenotypic heterogeneity in 22q11.2DS might be because of (1) the various sizes of the deletions and/or (2) rearrangements elsewhere on the genome -especially CNVs, mutations in candidate genes and changes in the three-dimensional structure of the genome that can lead to dysregulation of gene expression. Zeitz et al 40 found that longrange interactions in the COMT gene had an impact on phenotypic variability. The use of aCGH only covers the CNVs and maps deletion breakpoints.…”

Section: Discussionmentioning

confidence: 99%

A French multicenter study of over 700 patients with 22q11 deletions diagnosed using FISH or aCGH

Poirsier¹,

Besseau-Ayasse²,

Schluth-Bolard³

et al. 2015

Eur J Hum Genet

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Although 22q11.2 deletion syndrome (22q11.2DS) is the most recurrent human microdeletion syndrome associated with a highly variable phenotype, little is known about the condition's true incidence and the phenotype at diagnosis. We performed a multicenter, retrospective analysis of postnatally diagnosed patients recruited by members of the Association des Cytogénéticiens de Langue Française (the French-Speaking Cytogeneticists Association). Clinical and cytogenetic data on 749 cases diagnosed between 1995 and 2013 were collected by 31 French cytogenetics laboratories. The most frequent reasons for referral of postnatally diagnosed cases were a congenital heart defect (CHD, 48.6%), facial dysmorphism (49.7%) and developmental delay (40.7%). Since 2007 (the year in which array comparative genomic hybridization (aCGH) was introduced for the routine screening of patients with intellectual disability), almost all cases have been diagnosed using FISH (96.1%). Only 15 cases (all with an atypical phenotype) were diagnosed with aCGH; the deletion size ranged from 745 to 2904 kb. The deletion was inherited in 15.0% of cases and was of maternal origin in 85.5% of the latter. This is the largest yet documented cohort of patients with 22q11.2DS (the most commonly diagnosed microdeletion) from the same population. French cytogenetics laboratories diagnosed at least 108 affected patients (including fetuses) per year from among a national population of ∼ 66 million. As observed for prenatal diagnoses, CHDs were the most frequently detected malformation in postnatal diagnoses. The most common CHD in postnatal diagnoses was an isolated septal defect.

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Implications of COMT long-range interactions on the phenotypic variability of 22q11.2 deletion syndrome

Abstract: (2013) Implications of COMT long-range interactions on the phenotypic variability of 22q11.2 deletion syndrome, Nucleus, 4:6,[487][488][489][490][491][492][493]

Cited by 17 publications

References 38 publications

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

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

Oculo-auriculo-vertebral spectrum: Clinical and molecular analysis of 51 patients

A French multicenter study of over 700 patients with 22q11 deletions diagnosed using FISH or aCGH

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