Intragenic DOK7 deletion detected by whole-genome sequencing in congenital myasthenic syndromes

Yoshiteru Azuma, Ana Töpf, Teresinha Evangelista, Paulo José Lorenzoni, Andreas Roos, Pedro Viana, Hidehito Inagaki, Hiroki Kurahashi, Hanns Lochmüller

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Objective: To identify the genetic cause in a patient affected by ptosis and exercise-induced muscle weakness and diagnosed with congenital myasthenic syndromes (CMS) using whole-genome sequencing (WGS). Methods: Candidate gene screening and WGS analysis were performed in the case. Allele-specific PCR was subsequently performed to confirm the copy number variation (CNV) that was suspected from the WGS results. Results: In addition to the previously reported frameshift mutation c.1124-1127dup, an intragenic 6,261 bp deletion spanning from the 5′ untranslated region to intron 2 of the DOK7 gene was identified by WGS in the patient with CMS. The heterozygous deletion was suspected based on reduced coverage on WGS and confirmed by allele-specific PCR. The breakpoints had microhomology and an inverted repeat, which may have led to the development of the deletion during DNA replication. Conclusions: We report a CMS case with identification of the breakpoints of the intragenic DOK7 deletion using WGS analysis. This case illustrates that CNVs undetected by Sanger sequencing may be identified by WGS and highlights their relevance in the molecular diagnosis of a treatable neurologic condition such as CMS.

Original languageEnglish
Article numbere152
JournalNeurology: Genetics
Issue number3
Publication statusPublished - 01-07-2017

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Genetics(clinical)


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