Whole-exome sequencing and human leukocyte antigen analysis in familial myasthenia gravis with thymoma: Case report and literature review

Clin Neurol Neurosurg. 2021 Sep;208:106864. doi: 10.1016/j.clineuro.2021.106864. Epub 2021 Aug 3.


Myasthenia gravis (MG) is an autoimmune disease characterized by impaired neurotransmission at the neuromuscular junction. MG is generally non-inherited but is rarely inherited. Here, we report two patients with MG in the same pedigree: a 62-year-old Japanese man and his 46-year-old daughter who were positive for anti-acetylcholine receptor antibodies and had thymoma. We performed whole-exome sequencing (WES) and human leukocyte antigen (HLA) analyses to investigate the genetic contribution to familial onset. WES analysis of both patients showed no known variations in candidate genes for familial MG, and HLA analysis failed to detect HLA haplotypes seen in early-onset and late-onset MG. These findings suggest the presence of an unknown genetic background. Previous genetic studies on familial MG have identified ENOX1 and IFNGR1 as candidate genes in patients without thymoma, whereas no studies have identified candidate genes in patients with thymoma. To explore causative genes, it may be necessary to consider whether the genetic background differs between patients with and without thymoma in familial autoimmune MG.

Keywords: Familial myasthenia gravis; Human leukocyte antigen; Thymoma; Whole-exome sequencing.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Autoantibodies
  • Exome Sequencing
  • Female
  • HLA Antigens / genetics*
  • Humans
  • Male
  • Middle Aged
  • Myasthenia Gravis / genetics*
  • Myasthenia Gravis / immunology
  • Myasthenia Gravis / pathology
  • Pedigree
  • Receptors, Cholinergic / immunology
  • Thymoma / genetics*
  • Thymoma / immunology
  • Thymoma / pathology
  • Thymus Neoplasms / genetics*
  • Thymus Neoplasms / immunology
  • Thymus Neoplasms / pathology


  • Autoantibodies
  • HLA Antigens
  • Receptors, Cholinergic