%0 Journal Article
%T Recurrent Muscle Weakness with Rhabdomyolysis, Metabolic Crises, and Cardiac Arrhythmia Due to Bi-allelic TANGO2 Mutations
%A Adekunle Adesina
%A Angus Wilfong
%A Anita Inwood
%A Art Beaudet
%A Bradley£¿P. Coe
%A Brett Graham
%A Carlos£¿A. Bacino
%A Christina£¿Y. Miyake
%A Christine£¿M. Eng
%A David Coman
%A Donna£¿M. Muzny
%A Eric Boerwinkle
%A Fan Xia
%A Fernando Scaglia
%A Francesco Vetrini
%A Gary Clark
%A Gladys Zapata
%A Gustavo£¿H.B. Maegawa
%A Hope Northrup
%A James£¿R. Lupski
%A Jane Crosson
%A Jessica Duis
%A Jill£¿A. Rosenfeld
%A Jim McGill
%A Jordan£¿S. Orange
%A Laura£¿S. Farach
%A Levi£¿B. Watkin
%A Lisa Emrick
%A Magalie£¿S. Leduc
%A Mahshid Azamian
%A Marwan Shinawi
%A Mary£¿Kay Koenig
%A Mohammad£¿K. Eldomery
%A Nada Memon
%A Neil£¿A. Hanchard
%A Patricia Hernandez
%A Penelope£¿E. Bonnen
%A Pengfei Liu
%A Richard£¿A. Gibbs
%A Seema£¿R. Lalani
%A Shalini£¿N. Jhangiani
%A Shujuan Pan
%A Susan Schelley
%A Theodore Chiang
%A Timothy Lotze
%A Tomasz Gambin
%A Wenmiao Zhu
%A Yael Wilnai
%A Yan Ding
%A Zeynep£¿Hande£¿Coban Akdemir
%J Archive of "American Journal of Human Genetics".
%D 2016
%R 10.1016/j.ajhg.2015.12.008
%X 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¨C9 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¨C9. Additionally, a homozygous exons 4¨C6 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¨C9 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
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746334/