(Nakayama et al. 2018) Although 10-20% of patients with Dravet syndrome test negative for SCN1A mutations on standard tests, researchers have been able to identify mutations with improved testing methods. This study examined 230 cases of Dravet syndrome with apparently negative SCN1A results and found 2 mosaic microdeletions of the entire SCN1A gene. Mosaic mutations occur sometime after fertilization, after the first cell division. Theoretically, if the mutation occurs right after the first cell division, when there are only 2 cells, 50% of the patient’s cells (all that are descended from that mutated cell) will have the mutation, and 50% will not. Because embryonic cells differentiate into different classes of cells, that 50% estimation is not accurate, but “mosaic loads” describe the percentage of mutated alleles found in a patient. The two mosaic mutations found in the DS patients had extremely high mosaic load. In identifying 2 mosaic patients out of 230 cases (0.9%), the study highlights the importance of increasing testing quality.

Nakayama T, Ishii A, Yoshida T, Nasu H, Shimojima K, Yamamoto T, Kure S, Hirose S. Somatic mosaic deletions involving SCN1A cause Dravet syndrome. Am J Med Genet A. 2018 Mar;176(3):657-662. doi: 10.1002/ajmg.a.38596. Epub 2018 Jan 17. PubMed PMID: 29341473.