P.336 - MNDcap gene panel as a diagnostic tool in motor neuron disorders

Motor neuron disorders (MNDs) are a heterogeneous group of diseases that result from degeneration of motor neurons. Clinical and genetic overlap of MNDs is significant, however, and therefore diagnostics is challenging. MNDcap is a gene panel targeted to the exons of 275 genes that are known or predicted to cause motor neuron disease, hereditary neuropathy, spastic paraplegia or myasthenic syndrome. In our study, we have used MNDcap as a diagnostic tool for 157 MND patients whose diagnose had remained unsolved despite extensive studies. The sequencing data was processed using an in-house developed next-generation sequencing pipeline and the variants found were compared to the clinical findings. The results were classified in five categories: 1) diagnostic finding; 2) likely diagnostic finding; 3) possibly disease-related finding; 4) unlikely disease-related finding, and 5) no findings. In our patient cohort, the final diagnosis was reached in 20 patients (13 %), and in ten patients (6 %) the finding was likely diagnostic. Twenty-five patients (16 %) had a possibly disease-related finding, whereas 25 patients (16 %) had a finding that was unlikely disease-related, and 77 patients (49 %) did not have any clinically relevant findings. Altogether 13 different diagnoses were made, which reflects the complexity of the disease group. In this regard, MNDcap seems to be an effective diagnostic tool. However, the analysis method used does not detect repeat expansion mutations. Also potentially pathogenic deletions, insertions and inversions may not be detected, depending on their size. Therefore, it must be kept in mind, that quite common causes of MNDs, like the repeat expansion mutation in C9orf72 or the duplication of PMP22, cannot be detected by this method.