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 K Burton, Katherine H Kim, Leah Fleming, Rachel Westman, Peter Karachunski, Joline Dalton, Alice Basinger, Can Ficicioglu, Ingo Helbig & 12 others Manuela 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 journal › Article

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 K ; Kim, Katherine H ; 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.
@article{e1fc89b428664648b5fb7def054041cd,
title = "TANGO2: expanding the clinical phenotype and spectrum of pathogenic variants",
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",
author = "Dines, {Jennifer N.} and Katie Golden-Grant and Amy LaCroix and Muir, {Alison M.} and Cintr{\'o}n, {Dianne Laboy} and Kirsty McWalter and Cho, {Megan T.} and Angela Sun and Merritt, {J. Lawrence} and Jenny Thies and Dmitriy Niyazov and Burton, {Barbara K} and Kim, {Katherine H} and Leah Fleming and Rachel Westman and Peter Karachunski and Joline Dalton and Alice Basinger and Can Ficicioglu and Ingo Helbig and Manuela Pendziwiat and Hiltrud Muhle and Helbig, {Katherine L.} and Almuth Caliebe and Ren{\'e} Santer and Kolja Becker and Sharon Suchy and Ganka Douglas and Francisca Millan and Amber Begtrup and Monaghan, {Kristin G.} and Mefford, {Heather C.}",
year = "2019",
month = "3",
day = "1",
doi = "10.1038/s41436-018-0137-y",
language = "English (US)",
volume = "21",
pages = "601--607",
journal = "Genetics in Medicine",
issn = "1098-3600",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

Dines, JN, Golden-Grant, K, LaCroix, A, Muir, AM, Cintrón, DL, McWalter, K, Cho, MT, Sun, A, Merritt, JL, Thies, J, Niyazov, D, Burton, BK, Kim, KH, 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 K; Kim, Katherine H; 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 journal › Article

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 K

AU - Kim, Katherine H

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

UR - http://www.scopus.com/inward/record.url?scp=85053697540&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053697540&partnerID=8YFLogxK

U2 - 10.1038/s41436-018-0137-y

DO - 10.1038/s41436-018-0137-y

M3 - Article

VL - 21

SP - 601

EP - 607

JO - Genetics in Medicine

JF - Genetics in Medicine

SN - 1098-3600

IS - 3

ER -

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

Access to Document