TANGO2: expanding the clinical phenotype and spectrum of pathogenic variants

Jennifer N. Dines, Katie Golden-Grant, Amy LaCroix, Alison M. Muir, Dianne Laboy Cintrón, Kirsty McWalter, Megan T. Cho, Angela Sun, J. Lawrence Merritt, Jenny Thies, Dmitriy Niyazov, Barbara Burton, Katherine Kim, Leah Fleming, Rachel Westman, Peter Karachunski, Joline Dalton, Alice Basinger, Can Ficicioglu, Ingo HelbigManuela Pendziwiat, Hiltrud Muhle, Katherine L. Helbig, Almuth Caliebe, René Santer, Kolja Becker, Sharon Suchy, Ganka Douglas, Francisca Millan, Amber Begtrup, Kristin G. Monaghan, Heather C. Mefford*

*Corresponding author for this work

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)601-607
Number of pages7
JournalGenetics in Medicine
Volume21
Issue number3
DOIs
StatePublished - Mar 1 2019

Fingerprint

Exome
Phenotype
Genotype
Rhabdomyolysis
Brain Diseases
Intellectual Disability
Cardiac Arrhythmias
Seizures
Genes

Keywords

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

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Dines, J. N., Golden-Grant, K., LaCroix, A., Muir, A. M., Cintrón, D. L., McWalter, K., ... Mefford, H. C. (2019). TANGO2: expanding the clinical phenotype and spectrum of pathogenic variants. Genetics in Medicine, 21(3), 601-607. https://doi.org/10.1038/s41436-018-0137-y
Dines, Jennifer N. ; Golden-Grant, Katie ; LaCroix, Amy ; Muir, Alison M. ; Cintrón, Dianne Laboy ; McWalter, Kirsty ; Cho, Megan T. ; Sun, Angela ; Merritt, J. Lawrence ; Thies, Jenny ; Niyazov, Dmitriy ; Burton, Barbara ; Kim, Katherine ; Fleming, Leah ; Westman, Rachel ; Karachunski, Peter ; Dalton, Joline ; Basinger, Alice ; Ficicioglu, Can ; Helbig, Ingo ; Pendziwiat, Manuela ; Muhle, Hiltrud ; Helbig, Katherine L. ; Caliebe, Almuth ; Santer, René ; Becker, Kolja ; Suchy, Sharon ; Douglas, Ganka ; Millan, Francisca ; Begtrup, Amber ; Monaghan, Kristin G. ; Mefford, Heather C. / TANGO2 : expanding the clinical phenotype and spectrum of pathogenic variants. In: Genetics in Medicine. 2019 ; Vol. 21, No. 3. pp. 601-607.
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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.",
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Dines, JN, Golden-Grant, K, LaCroix, A, Muir, AM, Cintrón, DL, McWalter, K, Cho, MT, Sun, A, Merritt, JL, Thies, J, Niyazov, D, Burton, B, Kim, K, Fleming, L, Westman, R, Karachunski, P, Dalton, J, Basinger, A, Ficicioglu, C, Helbig, I, Pendziwiat, M, Muhle, H, Helbig, KL, Caliebe, A, Santer, R, Becker, K, Suchy, S, Douglas, G, Millan, F, Begtrup, A, Monaghan, KG & Mefford, HC 2019, 'TANGO2: expanding the clinical phenotype and spectrum of pathogenic variants', Genetics in Medicine, vol. 21, no. 3, pp. 601-607. https://doi.org/10.1038/s41436-018-0137-y

TANGO2 : expanding the clinical phenotype and spectrum of pathogenic variants. / Dines, Jennifer N.; Golden-Grant, Katie; LaCroix, Amy; Muir, Alison M.; Cintrón, Dianne Laboy; McWalter, Kirsty; Cho, Megan T.; Sun, Angela; Merritt, J. Lawrence; Thies, Jenny; Niyazov, Dmitriy; Burton, Barbara; Kim, Katherine; Fleming, Leah; Westman, Rachel; Karachunski, Peter; Dalton, Joline; Basinger, Alice; Ficicioglu, Can; Helbig, Ingo; Pendziwiat, Manuela; Muhle, Hiltrud; Helbig, Katherine L.; Caliebe, Almuth; Santer, René; Becker, Kolja; Suchy, Sharon; Douglas, Ganka; Millan, Francisca; Begtrup, Amber; Monaghan, Kristin G.; Mefford, Heather C.

In: Genetics in Medicine, Vol. 21, No. 3, 01.03.2019, p. 601-607.

Research output: Contribution to journalArticle

TY - JOUR

T1 - TANGO2

T2 - expanding the clinical phenotype and spectrum of pathogenic variants

AU - Dines, Jennifer N.

AU - Golden-Grant, Katie

AU - LaCroix, Amy

AU - Muir, Alison M.

AU - Cintrón, Dianne Laboy

AU - McWalter, Kirsty

AU - Cho, Megan T.

AU - Sun, Angela

AU - Merritt, J. Lawrence

AU - Thies, Jenny

AU - Niyazov, Dmitriy

AU - Burton, Barbara

AU - Kim, Katherine

AU - Fleming, Leah

AU - Westman, Rachel

AU - Karachunski, Peter

AU - Dalton, Joline

AU - Basinger, Alice

AU - Ficicioglu, Can

AU - Helbig, Ingo

AU - Pendziwiat, Manuela

AU - Muhle, Hiltrud

AU - Helbig, Katherine L.

AU - Caliebe, Almuth

AU - Santer, René

AU - Becker, Kolja

AU - Suchy, Sharon

AU - Douglas, Ganka

AU - Millan, Francisca

AU - Begtrup, Amber

AU - Monaghan, Kristin G.

AU - Mefford, Heather C.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - 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.

AB - 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.

KW - developmental delay DNA copy-number variation

KW - epilepsy

KW - exome sequencing

KW - intragenic deletion

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Dines JN, Golden-Grant K, LaCroix A, Muir AM, Cintrón DL, McWalter K et al. TANGO2: expanding the clinical phenotype and spectrum of pathogenic variants. Genetics in Medicine. 2019 Mar 1;21(3):601-607. https://doi.org/10.1038/s41436-018-0137-y