The intrafamilial variability of the 22q11.2 microduplication encompasses a spectrum from minor cognitive deficits to severe congenital anomalies

Rochebrochard, Céline de La; Joly‐Helas, Géraldine; Goldenberg, Alice; Durand, Isabelle; Laquerrière, Annie; Ickowicz, V.; Saugier-Veber, Pascale; Eurin, D; Moirot, H.; Diguet, Alain; Kergal, Fabrice de; Tiercin, Coralie; Macé, Bertrand; Marpeau, Loïc; Frébourg, Thierry

doi:10.1002/ajmg.a.31227

Cited by 66 publications

(84 citation statements)

References 16 publications

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“…The phenotype of both syndromes is variable, with shared clinical anomalies that include heart defects, urogenital abnormalities, and velopharyngeal insufficiency. [27][28][29] The incidence of the DiGeorge syndrome is estimated to be 1 case in 4000 births. 30 The 22q11.2 microduplication syndrome appears to be less prevalent.…”

Section: Discussionmentioning

confidence: 99%

Karyotype Versus Microarray Testing for Genetic Abnormalities After Stillbirth

Reddy

Page

Saade

et al. 2013

Obstetrical &Amp; Gynecological Survey

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Section: Discussionmentioning

confidence: 99%

Karyotype Versus Microarray Testing for Genetic Abnormalities After Stillbirth

Reddy

Page

Saade

et al. 2013

Obstetrical &Amp; Gynecological Survey

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“…9,39 In general, there seems to be variable expressivity between family members carrying the common ϳ3-Mb and ϳ1.5-Mb microduplications (to the extent that transmitting parents escaped clinical detection before their child's diagnosis), but virtually all of the individuals carrying these duplications had some degree of developmental delay. A recent report of an antenatal case of 22q11.2 duplication associated with severe cardiovascular anomalies, including total anomalous pulmonary venous return and heterotaxy, inherited from a father with mild cognitive deficits 42 highlights the potential for extreme variability of phenotypes seen in patients with 22q11.2 duplications even within a family.…”

Section: Discussionmentioning

confidence: 99%

Microduplications of 22q11.2 are frequently inherited and are associated with variable phenotypes

Berg

Yonath

et al. 2008

Genetics in Medicine

172

173

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Purpose: Genomic rearrangements of chromosome 22q11.2, including the microdeletion associated with DiGeorge/velocardiofacial syndrome, are mediated by nonallelic homologous recombination between region-specific low-copy repeats. To date, only a small number of patients with 22q11.2 microduplication have been identified. Methods:We report the identification by array-comparative genomic hybridization of 14 individuals from eight families who harbor microduplications within the 22q11.2 region. Results: We have now observed a variety of microduplications, including the typical common ϳ3-Mb microduplication, ϳ1.5-Mb nested duplication, and smaller microduplications within and distal to the DiGeorge/velocardiofacial syndrome region, consistent with nonallelic homologous recombination using distinct low-copy repeats in the 22q11.2 DiGeorge/velocardiofacial syndrome region. These microduplications likely represent the predicted reciprocal rearrangements to the microdeletions characterized in the 22q11.2 region. The phenotypes seen in these individuals are generally mild and highly variable; familial transmission is frequently observed. Conclusions: These findings highlight the unbiased ability of array-comparative genomic hybridization to identify genomic imbalances and further define the molecular etiology and clinical phenotypes seen in microduplication 22q11.2 syndrome. Our findings also further support that the 22q11.2 region is highly dynamic with frequent rearrangements using alternative low-copy repeats as recombination substrates. Genet Med 2008:10(4):267-277.

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“…In theory, these events should occur with equal frequency. However, reports of the 22q11.2 duplication syndrome have been quite rare in comparison with the del22q11 syndrome [4][5][6] .…”

Section: Tof -Tetralogy Of Fallot; Lhh -Left Heart Hypoplasia; Tga -Tmentioning

confidence: 99%

“…Some authors have speculated that, probably, the 22q11.2 duplication is being underdiagnosed, due to its great clinical variability and technical difficulties [2][3][4][5][6][7][8] . Most of the duplications are microscopic (microduplications) and thus, they escape detection at the routine chromosomal analysis.…”

Section: Tof -Tetralogy Of Fallot; Lhh -Left Heart Hypoplasia; Tga -Tmentioning

confidence: 99%

“…It is known that the region q11.2 of chromosome 22 presents a non-usual rearrangement, with regions of low-copy number repeats which, during meiosis, predispose to a pairing error between the chromosomes and, consequently, to an unequal crossing-over, which can lead to a deletion (del22q11) or a duplication of the q11.2 rgion [2][3][4] . The latter condition was recently identified and has been characterized by an extremely variable phenotypic spectrum, which includes the presence, among many abnormalities, of congenital cardiac defects [4][5][6] . However, the actual frequency of these malformations is still unknown in individuals with the 22q11.2 duplication, as well as the frequency of this duplication in patients with congenital cardiopathy 3 …”

Section: Introductionmentioning

confidence: 99%

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