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.
Bibliographical noteFunding Information:
We thank the families, GeneDx, and practitioners for their participation and collaboration in this case series. Research reported in this publication was supported in part by a grant from the National Institutes of Health (NS069605 to H.C.M.), and the National Institute of General Medical Sciences of the National Institutes of Health Postdoctoral Training Program in Medical Genetics (5T32GM007454 to J.N.D.). This work was also supported by intramural funds of the University of Kiel (I.H.), the German Research Foundation (HE5415/3-1 to I.H.) within the EuroEPINOMICS framework of the European Science Foundation, and individual grants by the German Research Foundation (D.F. G., HE5415/5-1, HE5415/6-1 to I.H.).
- developmental delay DNA copy-number variation
- exome sequencing
- intragenic deletion
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, U.S. Gov't, Non-P.H.S.