Transmitted duplication of 12q21.32–12q22 includes 48 genes and has no apparent phenotypic consequences

Barber, John; Maloney, Viv; Kirchhoff, Maria; Thomas, N. Simon; Boyle, Tracy A.; Castle, Bruce

doi:10.1002/ajmg.a.31614

Cited by 4 publications

(2 citation statements)

References 11 publications

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“…One has a large de novo 12q21.1q21.33 duplication, identified by array CGH and confirmed by standard karyotyping. Interstitial 12q duplications are very rare and can have little or no phenotypic effect: Barber et al [2007] described a large transmitted duplication of 12q with partial overlap to the one we describe here that had no apparent clinical consequences. Truly, this patient is mildly affected and has no overt ID.…”

Section: Discussionmentioning

confidence: 58%

Novel Mutations and Unreported Clinical Features in KBG Syndrome

Scarano¹,

Tassone²,

Graziano

et al. 2019

Mol Syndromol

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KBG syndrome is an autosomal dominant disorder caused by pathogenic variants within ANKRD11 or deletions of 16q24.3 which include ANKRD11. It is characterized by distinctive facial features, developmental delay, short stature, and skeletal anomalies. We report 12 unrelated patients where a clinical diagnosis of KBG was suspected and confirmed by targeted analyses. Nine patients showed a point mutation in ANKRD11 (none of which were previously reported) and 3 carried a 16q24.3 deletion. All patients presented with typical facial features and macrodontia. Skeletal abnormalities were constant, and the majority of patients showed joint stiffness. Three patients required growth hormone treatment with a significant increase of height velocity. Brain malformations were identified in 8 patients. All patients showed behavioral abnormalities and most had developmental delay. Two patients had hematological abnormalities. We emphasize that genetic analysis of ANKRD11 can easily reach a detection rate higher than 50% thanks to clinical phenotyping, although it is known that a subset of ANKRD11-mutated patients show very mild features and will be more easily identified through the implementation of gene panels or exome sequencing. Joint stiffness was reported previously in few patients, but it seems to be a common feature and can be helpful for the diagnosis. Hematological abnormalities could be present and warrant a specific follow-up.

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Section: Discussionmentioning

confidence: 58%

Novel Mutations and Unreported Clinical Features in KBG Syndrome

Scarano¹,

Tassone²,

Graziano

et al. 2019

Mol Syndromol

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show abstract

“…The structural variants can impact gene function 8,35 (or not 46 ) in several ways. They can create functional loss through deletion or disruption of one or more genes, behaving as dominant or recessive alleles according to the cellular function of the impacted gene product(s).…”

Section: Technology and Databasesmentioning

confidence: 99%

Contemplating effects of genomic structural variation

Buchanan

Scherer

2008

Genetics in Medicine

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Two developments have sparked new directions in the genetics-to-genomics transition for research and medical applications: the advance of whole-genome assays by array or DNA sequencing technologies, and the discovery among human genomes of extensive submicroscopic genomic structural variation, including copy number variation.For health care to benefit from interpretation of genomic data, we need to know how these variants contribute to the phenotype of the individual. Research is revealing the spectrum, both in size and complexity, of structural genotypic variation, and its association with a broad range of human phenotypes. Genomic disorders associated with relatively large, recurrent contiguous variants have been recognized for some time, as have certain Mendelian traits associated with functional disruption of single genes by structural variation. More recent examples from phenotype-and genotype-driven studies demonstrate a greater level of complexity, with evidence of incremental dosage effects, gene interaction networks, buffering and modifiers, and position effects. Mechanisms underlying such variation are emerging to provide a handle on the bulk of human variation, which is associated with complex traits and adaptive potential. Interpreting genotypes for personalized health care and communicating knowledge to the individual will be significant challenges for genomics professionals. Genet Med 2008:10(9):639 -647.

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2014

Benign &Amp; Pathological Chromosomal Imbalances

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Transmitted duplication of 12q21.32–12q22 includes 48 genes and has no apparent phenotypic consequences

Cited by 4 publications

References 11 publications

Novel Mutations and Unreported Clinical Features in KBG Syndrome

Novel Mutations and Unreported Clinical Features in KBG Syndrome

Contemplating effects of genomic structural variation

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