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 G Engel, Hakon Hakonarson, John Christodoulou, Xun Xu

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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
Volume25
Issue number3
DOIs
StatePublished - Mar 1 2015

Fingerprint

Congenital Myasthenic Syndromes
Delayed Diagnosis
Exome
Enzymes
Mitochondrial Myopathies
Genes
Phenotype
Mitochondrial Diseases
Dystrophin
Mutation
Multiplex Polymerase Chain Reaction
Acetylcholinesterase
Exons
Collagen
Health

Keywords

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

ASJC Scopus subject areas

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

Cite this

Guo, Y., Menezes, M. J., Menezes, M. P., Liang, J., Li, D., Riley, L. G., ... Xu, X. (2015). Delayed diagnosis of congenital myasthenia due to associated mitochondrial enzyme defect. Neuromuscular Disorders, 25(3), 257-261. https://doi.org/10.1016/j.nmd.2014.11.017

Delayed diagnosis of congenital myasthenia due to associated mitochondrial enzyme defect. / Guo, Yiran; Menezes, Minal J.; Menezes, Manoj P.; Liang, Jinlong; Li, Dong; Riley, Lisa G.; Clarke, Nigel F.; Andrews, P. Ian; Tian, Lifeng; Webster, Richard; Wang, Fengxiang; Liu, Xuanzhu; Shen, Yulan; Thorburn, David R.; Keating, Brendan J.; Engel, Andrew G; Hakonarson, Hakon; Christodoulou, John; Xu, Xun.

In: Neuromuscular Disorders, Vol. 25, No. 3, 01.03.2015, p. 257-261.

Research output: Contribution to journalArticle

Guo, Y, Menezes, MJ, Menezes, MP, Liang, J, Li, D, Riley, LG, Clarke, NF, Andrews, PI, Tian, L, Webster, R, Wang, F, Liu, X, Shen, Y, Thorburn, DR, Keating, BJ, Engel, AG, Hakonarson, H, Christodoulou, J & Xu, X 2015, 'Delayed diagnosis of congenital myasthenia due to associated mitochondrial enzyme defect', Neuromuscular Disorders, vol. 25, no. 3, pp. 257-261. https://doi.org/10.1016/j.nmd.2014.11.017
Guo, Yiran ; Menezes, Minal J. ; Menezes, Manoj P. ; Liang, Jinlong ; Li, Dong ; Riley, Lisa G. ; Clarke, Nigel F. ; Andrews, P. Ian ; Tian, Lifeng ; Webster, Richard ; Wang, Fengxiang ; Liu, Xuanzhu ; Shen, Yulan ; Thorburn, David R. ; Keating, Brendan J. ; Engel, Andrew G ; Hakonarson, Hakon ; Christodoulou, John ; Xu, Xun. / Delayed diagnosis of congenital myasthenia due to associated mitochondrial enzyme defect. In: Neuromuscular Disorders. 2015 ; Vol. 25, No. 3. pp. 257-261.
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