Bi-allelic TANGO2 mutations were identified as the genetic etiology in 12 subjects with episodic rhabdomyolysis, metabolic crises, and cardiac arrhythmias.
Observational (n=12)
Bi-allelic mutations in TANGO2 are a recurrent pathogenic cause of episodic rhabdomyolysis, metabolic crises, and life-threatening cardiac tachyarrhythmias.
The underlying genetic etiology of rhabdomyolysis remains elusive in a significant fraction of individuals presenting with recurrent metabolic crises and muscle weakness. Using exome sequencing, we identified bi-allelic mutations in TANGO2 encoding transport and Golgi organization 2 homolog (Drosophila) in 12 subjects with episodic rhabdomyolysis, hypoglycemia, hyperammonemia, and susceptibility to life-threatening cardiac tachyarrhythmias. A recurrent homozygous c.460G>A (p.Gly154Arg) mutation was found in four unrelated individuals of Hispanic/Latino origin, and a homozygous ∼34 kb deletion affecting exons 3-9 was observed in two families of European ancestry. One individual of mixed Hispanic/European descent was found to be compound heterozygous for c.460G>A (p.Gly154Arg) and the deletion of exons 3-9. Additionally, a homozygous exons 4-6 deletion was identified in a consanguineous Middle Eastern Arab family. No homozygotes have been reported for these changes in control databases. Fibroblasts derived from a subject with the recurrent c.460G>A (p.Gly154Arg) mutation showed evidence of increased endoplasmic reticulum stress and a reduction in Golgi volume density in comparison to control. Our results show that the c.460G>A (p.Gly154Arg) mutation and the exons 3-9 heterozygous deletion in TANGO2 are recurrent pathogenic alleles present in the Latino/Hispanic and European populations, respectively, causing considerable morbidity in the homozygotes in these populations.
Lalani et al. (Thu,) conducted a observational in Episodic rhabdomyolysis, hypoglycemia, hyperammonemia, and susceptibility to life-threatening cardiac tachyarrhythmias (n=12). Bi-allelic TANGO2 mutations vs. Control databases and control fibroblasts was evaluated on Identification of genetic etiology. Bi-allelic TANGO2 mutations were identified as the genetic etiology in 12 subjects with episodic rhabdomyolysis, metabolic crises, and cardiac arrhythmias.