Detection of an Atypical 22q11 Deletion That Has No Overlap with the DiGeorge Syndrome Critical Region

O'Donnell, Hilary; McKeown, Carole; Gould, C. P.; Morrow, Bernice E.; Scambler, Peter J.

doi:10.1016/s0002-9297(07)64250-5

Cited by 55 publications

(32 citation statements)

References 14 publications

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“…[8][9][10][11][12][13][14] These are either nested within the large 3 Mb typical deleted region, or they are distal to and do not overlap with it. The phenotype of patients with distal deletions not overlapping the minimal DiGeorge critical region seems to be indistinguishable from that of patients with the common large deletion.…”

Section: Discussionmentioning

confidence: 99%

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A novel atypical 22q11.2 distal deletion in father and son

García‐Miñaúr¹,

Fantes²,

Murray³

et al. 2002

Journal of Medical Genetics

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Section: Discussionmentioning

confidence: 99%

“…7 However, to date seven patients have been reported with atypical deletions that show no overlap with this critical region. [8][9][10][11][12][13][14] These cases are extremely valuable as they may provide some insight into the underlying molecular mechanisms and may help to identify potential gene(s) involved.…”

mentioning

confidence: 99%

A novel atypical 22q11.2 distal deletion in father and son

García‐Miñaúr¹,

Fantes²,

Murray³

et al. 2002

Journal of Medical Genetics

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“…Patients with clinically similar phenotypes have been found with non-overlapping deletions within 22q11.2 (Amati et al, 1999; McQuade et al, 1999; O'Donnell et al, 1997; Scambler, 2000). Therefore, the human deletion map has not been helpful in identifying candidate genes (Lindsay et al, 2001).…”

Section: Cardiac Congenital Abnormalities Involving the Neural Crest mentioning

confidence: 94%

The neural crest in cardiac congenital anomalies

2012

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This review discusses the function of neural crest as they relate to cardiovascular defects. The cardiac neural crest cells are a subpopulation of cranial neural crest discovered nearly 30 years ago by ablation of premigratory neural crest. The cardiac neural crest cells are necessary for normal cardiovascular development. We begin with a description of the crest cells in normal development, including their function in remodeling the pharyngeal arch arteries, outflow tract septation, valvulogenesis, and development of the cardiac conduction system. The cells are also responsible for modulating signaling in the caudal pharynx, including the second heart field. Many of the molecular pathways that are known to influence specification, migration, patterning and final targeting of the cardiac neural crest cells are reviewed. The cardiac neural crest cells play a critical role in the pathogenesis of various human cardiocraniofacial syndromes such as DiGeorge, Velocardiofacial, CHARGE, Fetal Alcohol, Alagille, LEOPARD, and Noonan syndromes, as well as Retinoic Acid Embryopathy. The loss of neural crest cells or their dysfunction may not always directly cause abnormal cardiovascular development, but are involved secondarily because crest cells represent a major component in the complex tissue interactions in the head, pharynx and outflow tract. Thus many of the human syndromes linking defects in the heart, face and brain can be better understood when considered within the context of a single cardiocraniofacial developmental module with the neural crest being a key cell type that interconnects the regions.

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“…[6][7][8] Furthermore, Kurahashi et al 9 investigated 100 patients with several fluorescent in situ hybridisation (FISH) probes from the 3 Mb region and detected a small distally nested deletion in one patient. A few patients with typical phenotype but normal results for the commonly used probes were further investigated and reported to have atypical nested deletions, [10][11][12][13][14] but also adjacent atypical distal deletions. 15 16 As both common and atypical deletions were shown to be mediated by several low copy repeats (LCR) within the region, 6 15 17 18 we suspected that, if investigated systematically, atypical deletions would be revealed to be more common than reported.…”

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confidence: 99%

Systematic assessment of atypical deletions reveals genotype-phenotype correlation in 22q11.2

Rauch¹,

Zink²,

Zweier³

et al. 2005

Journal of Medical Genetics

123

153

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Introduction: Clinical variability associated with the common 22q11.2 microdeletion is well known, and has led to a broad application of FISH diagnostics with probes for loci TUPLE1 or D22S75 (N25), although, rarely reported atypical deletions associated with the same phenotypic spectrum would not be discovered by these probes. As most types of 22q11.2 deletions occur between low copy repeats within the region (LCR22), we assumed that atypical deletions should be more common than has been reported. To address this question and the possibility of a deletion size related genotype-phenotype correlation, we systematically assessed the frequency of typical and atypical 22q11.2 deletions in a large cohort of patients. Methods: We used a set of 10 fluorescent in situ hybridisation (FISH) DNA probes, capable of detecting all reported and hypothetical deletions between the LCR22, and analysed 350 patients. Deletion sizes in atypical deletions were established by use of further FISH probes. Frequency of certain atypical deletions was analysed in controls by FISH and quantitative PCR. Results: Patients with conotruncal heart defects (ctCHD) and with typical VCFS phenotype showed the common 3 Mb or nested 1.5 Mb deletions (in 18.5% and 78.6%, respectively), but no atypical deletion, while 5% (3/63) of patients with a mildly suggestive, atypical phenotype showed atypical distal deletions, which were not detected in patients with mental retardation of unknown origin or in healthy controls. Discussion: These statistically significant differences demonstrate that atypical distal 22q11.2 deletions are very uncommon in patients with ctCHDs, while atypical congenital heart defects and mild dysmorphism are recognisable feature of atypical distal deletions. Further phenotype-genotype analysis disclosed association of significant developmental delay with the distal part of the common deletion region, and choanal atresia and atypical CHDs with the adjacent distal deletion region.

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Detection of an Atypical 22q11 Deletion That Has No Overlap with the DiGeorge Syndrome Critical Region

Cited by 55 publications

References 14 publications

A novel atypical 22q11.2 distal deletion in father and son

A novel atypical 22q11.2 distal deletion in father and son

The neural crest in cardiac congenital anomalies

Systematic assessment of atypical deletions reveals genotype-phenotype correlation in 22q11.2

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