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Genet Med. 2019 Mar;21(3):601-607. doi: 10.1038/s41436-018-0137-y. Epub 2018 Sep 24.

TANGO2: expanding the clinical phenotype and spectrum of pathogenic variants.

Author information

1
Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington, USA.
2
Division of Genetic Medicine, Seattle Children's Hospital, Seattle, Washington, USA.
3
Department of Pediatrics, University of Washington, Seattle, Washington, USA.
4
GeneDx, Gaithersburg, Maryland, USA.
5
Division of Medical Genetics, Ochsner Health System and University of Queensland, Brisbane, Australia.
6
Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg SOM, Chicago, Illinois, USA.
7
Genetics and Metabolic Clinic, St. Luke's Children's Hospital System, Boise, Idaho, USA.
8
Department of Neurology, University of Minnesota, Minneapolis, Minnesota, USA.
9
Cook's Children Genetic Center, Fort Worth, Texas, USA.
10
Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
11
Department of Neuropediatrics, Universitätsklinikum Schleswig Holstein Campus Kiel, Kiel, Germany.
12
Institute for Human Genetics, Universitätsklinikum Schleswig Holstein Campus Kiel, Kiel, Germany.
13
Department of Pediatrics, University Medical Center Eppendorf, Hamburg, Germany.
14
Department of Pediatrics, University of Washington, Seattle, Washington, USA. hmefford@uw.edu.

Abstract

PURPOSE:

TANGO2-related disorders were first described in 2016 and prior to this publication, only 15 individuals with TANGO2-related disorder were described in the literature. Primary features include metabolic crisis with rhabdomyolysis, encephalopathy, intellectual disability, seizures, and cardiac arrhythmias. We assess whether genotype and phenotype of TANGO2-related disorder has expanded since the initial discovery and determine the efficacy of exome sequencing (ES) as a diagnostic tool for detecting variants.

METHODS:

We present a series of 14 individuals from 11 unrelated families with complex medical and developmental histories, in whom ES or microarray identified compound heterozygous or homozygous variants in TANGO2.

RESULTS:

The initial presentation of patients with TANGO2-related disorders can be variable, including primarily neurological presentations. We expand the phenotype and genotype for TANGO2, highlighting the variability of the disorder.

CONCLUSION:

TANGO2-related disorders can have a more diverse clinical presentation than previously anticipated. We illustrate the utility of routine ES data reanalysis whereby discovery of novel disease genes can lead to a diagnosis in previously unsolved cases and the need for additional copy-number variation analysis when ES is performed.

KEYWORDS:

developmental delay DNA copy-number variation; epilepsy; exome sequencing; intragenic deletion

PMID:
30245509
PMCID:
PMC6752277
DOI:
10.1038/s41436-018-0137-y
[Indexed for MEDLINE]
Free PMC Article

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