Delayed diagnosis of congenital myasthenia due to associated mitochondrial enzyme defect

Yiran Guo, Minal J. Menezes, Manoj P. Menezes, Jinlong Liang, Dong Li, Lisa G. Riley, Nigel F. Clarke, P. Ian Andrews, Lifeng Tian, Richard Webster, Fengxiang Wang, Xuanzhu Liu, Yulan Shen, David R. Thorburn, Brendan J. Keating, Andrew Engel, Hakon Hakonarson, John Christodoulou, Xun Xu

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Clinical phenotypes of congenital myasthenic syndromes and primary mitochondrial disorders share significant overlap in their clinical presentations, leading to challenges in making the correct diagnosis. Next generation sequencing is transforming molecular diagnosis of inherited neuromuscular disorders by identifying novel disease genes and by identifying previously known genes in undiagnosed patients. This is evident in two patients who were initially suspected to have a mitochondrial myopathy, but in whom a clear diagnosis of congenital myasthenic syndromes was made through whole exome sequencing. In patient 1, whole exome sequencing revealed compound heterozygous mutations c.1228C > T (p.Arg410Trp) and c.679C > T (p.Arg227*) in collagen-like tail subunit (single strand of homotrimer) of asymmetric acetylcholinesterase (. COLQ). In patient 2, in whom a deletion of exon 52 in Dystrophin gene was previously detected by multiplex ligation-dependent probe amplification, Sanger sequencing revealed an additional homozygous mutation c.1511_1513delCTT (p.Pro504Argfs*183) in docking protein7 (DOK7). These case reports highlight the need for careful diagnosis of clinically heterogeneous syndromes like congenital myasthenic syndromes, which are treatable, and for which delayed diagnosis is likely to have implications for patient health. The report also demonstrates that whole exome sequencing is an effective diagnostic tool in providing molecular diagnosis in patients with complex phenotypes.

Original languageEnglish (US)
Pages (from-to)257-261
Number of pages5
JournalNeuromuscular Disorders
Issue number3
StatePublished - Mar 1 2015


  • COLQ
  • Congenital myasthenia
  • DOK7
  • Duchenne muscular dystrophy
  • Mitochondrial respiratory chain
  • Mutation
  • Whole exome sequencing

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Neurology
  • Clinical Neurology
  • Genetics(clinical)


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