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 language | English (US) |
|---|---|
| Pages (from-to) | 601-607 |
| Number of pages | 7 |
| Journal | Genetics in Medicine |
| Volume | 21 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2019 |
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Keywords
- developmental delay DNA copy-number variation
- epilepsy
- exome sequencing
- intragenic deletion
ASJC Scopus subject areas
- Genetics(clinical)
Cite this
}
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 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
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
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
C2 - 30245509
AN - SCOPUS:85053697540
VL - 21
SP - 601
EP - 607
JO - Genetics in Medicine
JF - Genetics in Medicine
SN - 1098-3600
IS - 3
ER -