Kleyner, R., Malcolmson, J., Tegay, D., Ward, K., Maughan, A., Maughan, G., Nelson, L., Wang, K., Robison, R., Lyon, G. J. (November 2016) KBG syndrome involving a single-nucleotide duplication in ANKRD11. Cold Spring Harb Mol Case Stud, 2 (6). a001131. ISSN 2373-2873 (Linking)
Abstract
KBG syndrome is a rare autosomal dominant genetic condition characterized by neurological involvement and distinct facial, hand, and skeletal features. More than 70 cases have been reported; however, it is likely that KBG syndrome is underdiagnosed because of lack of comprehensive characterization of the heterogeneous phenotypic features. We describe the clinical manifestations in a male currently 13 years of age, who exhibited symptoms including epilepsy, severe developmental delay, distinct facial features, and hand anomalies, without a positive genetic diagnosis. Subsequent exome sequencing identified a novel de novo heterozygous single base pair duplication (c.6015dupA) in ANKRD11, which was validated by Sanger sequencing. This single-nucleotide duplication is predicted to lead to a premature stop codon and loss of function in ANKRD11, thereby implicating it as contributing to the proband's symptoms and yielding a molecular diagnosis of KBG syndrome. Before molecular diagnosis, this syndrome was not recognized in the proband, as several key features of the disorder were mild and were not recognized by clinicians, further supporting the concept of variable expressivity in many disorders. Although a diagnosis of cerebral folate deficiency has also been given, its significance for the proband's condition remains uncertain.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | absent speech autism bilateral single transverse palmar creases broad nasal tip clinodactyly of the 5th finger developmental regression generalized tonic-clonic seizures on awakening intellectual disability, moderate low CSF 5-methyltetrahydrofolate pes planus short philtrum short toe |
| Subjects: | diseases & disorders > congenital hereditary genetic diseases bioinformatics > genomics and proteomics > annotation > phenotyping bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > single nucleotide polymorphism |
| CSHL Authors: | |
| Communities: | CSHL labs > Lyon lab |
| Depositing User: | Matt Covey |
| Date: | November 2016 |
| Date Deposited: | 08 Dec 2016 17:21 |
| Last Modified: | 10 Jan 2018 17:10 |
| PMCID: | PMC5111005 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/33929 |
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