22q11 Deletion Syndrome

Fernandez, Alejandra; Meechan, Daniel W.; Baker, Jennifer L.; Karpinski, Beverly A.; LaMantia, Anthony‐Samuel; Maynard, Thomas M.

doi:10.1016/b978-0-12-405945-0.00036-3

Cited by 2 publications

(1 citation statement)

References 104 publications

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“…The common 22q11.2 deletion syndrome is proposed to be one of the most common microdeletion syndromes [ 3 , 4 ]. The incidence is estimated to 1 : 2,000–4,000 live births [ 5 , 6 ]. However, the central microdeletions are rare and known to have reduced penetrance and variable expression.…”

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confidence: 99%

Total Anomalous Pulmonary Venous Connection in Mother and Son with a Central 22q11.2 Microdeletion

Faurschou

Lildballe

Maroun

et al. 2021

Case Reports in Genetics

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In this clinical report, we describe a male infant and his mother, who had similar congenital heart defects. They were both diagnosed neonatally with total anomalous pulmonary venous connection (TAPVC) in combination with other heart defects. Neither of the two had any other organ malformations or dysmorphic facial features. SNP-array identified a central 22q11.2 microdeletion in the male infant and his mother as well as in the maternal grandmother and maternal aunt. The mother and the maternal aunt additionally harbored a 15q11.2 BP1-BP2 microdeletion. The maternal grandmother was unaffected by heart disease. However, heart computed tomography scan of the maternal aunt revealed a quadricuspid aortic valve. Additionally, the maternal grandmother and the maternal aunt both had significant learning disabilities. Rarely, TAPVC has been described in patients with the common 22q11.2 microdeletions. However, to the best of our knowledge, TAPVC has not previously been reported in patients with this small central 22q11.2 microdeletion. Haploinsufficiency of TBX1 was originally thought to be the main cause of the 22q11.2 microdeletion syndrome phenotype, but TBX1 is not included in the atypical central 22q11.2 microdeletion. Previous reports have suggested an association between TAPVC and the 15q11.2 BP1-BP2 microdeletion. Our report does not support this association as the maternal aunt, who harbors both microdeletions, is unaffected by TAPVC, and the male infant affected by TAPVC does not harbor the 15q11.2 BP1-BP2 microdeletion. Our findings support that genes located in the central 22q11.2 region are important for heart development and that haploinsufficiency of these genes plays a crucial role in the development of the rare heart defect TAPVC.

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Section: Introductionmentioning

confidence: 99%

Total Anomalous Pulmonary Venous Connection in Mother and Son with a Central 22q11.2 Microdeletion

Faurschou

Lildballe

Maroun

et al. 2021

Case Reports in Genetics

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In the line-up: deleted genes associated with DiGeorge/22q11.2 deletion syndrome: are they all suspects?

Motahari

Moody

Maynard

et al. 2019

J Neurodevelop Disord

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Background 22q11.2 deletion syndrome (22q11DS), a copy number variation (CNV) disorder, occurs in approximately 1:4000 live births due to a heterozygous microdeletion at position 11.2 (proximal) on the q arm of human chromosome 22 (hChr22) (McDonald-McGinn and Sullivan, Medicine 90:1-18, 2011). This disorder was known as DiGeorge syndrome, Velo-cardio-facial syndrome (VCFS) or conotruncal anomaly face syndrome (CTAF) based upon diagnostic cardiovascular, pharyngeal, and craniofacial anomalies (McDonald-McGinn and Sullivan, Medicine 90:1-18, 2011; Burn et al., J Med Genet 30:822-4, 1993) before this phenotypic spectrum was associated with 22q11.2 CNVs. Subsequently, 22q11.2 deletion emerged as a major genomic lesion associated with vulnerability for several clinically defined behavioral deficits common to a number of neurodevelopmental disorders (Fernandez et al., Principles of Developmental Genetics, 2015; Robin and Shprintzen, J Pediatr 147:90-6, 2005; Schneider et al., Am J Psychiatry 171:627-39, 2014). Results The mechanistic relationships between heterozygously deleted 22q11.2 genes and 22q11DS phenotypes are still unknown. We assembled a comprehensive “line-up” of the 36 protein coding loci in the 1.5 Mb minimal critical deleted region on hChr22q11.2, plus 20 protein coding loci in the distal 1.5 Mb that defines the 3 Mb typical 22q11DS deletion. We categorized candidates based upon apparent primary cell biological functions. We analyzed 41 of these genes that encode known proteins to determine whether haploinsufficiency of any single 22q11.2 gene—a one gene to one phenotype correspondence due to heterozygous deletion restricted to that locus—versus complex multigenic interactions can account for single or multiple 22q11DS phenotypes. Conclusions Our 22q11.2 functional genomic assessment does not support current theories of single gene haploinsufficiency for one or all 22q11DS phenotypes. Shared molecular functions, convergence on fundamental cell biological processes, and related consequences of individual 22q11.2 genes point to a matrix of multigenic interactions due to diminished 22q11.2 gene dosage. These interactions target fundamental cellular mechanisms essential for development, maturation, or homeostasis at subsets of 22q11DS phenotypic sites. Electronic supplementary material The online version of this article (10.1186/s11689-019-9267-z) contains supplementary material, which is available to authorized users.

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22q11 Deletion Syndrome

Cited by 2 publications

References 104 publications

Total Anomalous Pulmonary Venous Connection in Mother and Son with a Central 22q11.2 Microdeletion

Total Anomalous Pulmonary Venous Connection in Mother and Son with a Central 22q11.2 Microdeletion

In the line-up: deleted genes associated with DiGeorge/22q11.2 deletion syndrome: are they all suspects?

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