Investigation for RAPSN and DOK-7 mutations in a cohort of seronegative myasthenia gravis patients

Introduction: Myasthenia gravis (MG) is an autoimmune disease. Patients without detectable antibodies against the nicotinic acetylcholine receptor or the muscle‐specific tyrosine kinase are referred to as seronegative MG (SNMG). Because late‐onset congenital myasthenic syndromes (CMSs) due to RAPSN or DOK7 mutations may be mistaken for SNMG, we investigated their frequency in a nationwide SNMG cohort. Methods: We performed sequencing of RAPSN and DOK7 in all Norwegian SNMG patients (n = 74) and 37 healthy controls, examining for the N88K and c.1124_1127dupTGCC mutations, respectively. Results: We found 1 patient homozygous for N88K and 2 carriers of the N88K mutation. Sequencing of DOK7 revealed no mutations. Conclusions: This study confirms that rapsn CMS can be mistaken for SNMG. In addition, the frequency of rapsn CMS in our nationwide SNMG cohort was found to be low. SNMG patients with an atypical clinical presentation and pediatric cases should be tested for the N88K mutation before initiation of immunosuppressive drug treatment or thymectomy. Muscle Nerve, 2011