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A novel missense SNAP25b mutation in two affected siblings from an Israeli family showing seizures and cerebellar ataxia


SNAP25 is a core component of the soluble N-ethylmaleimide-sensitive factor attachment receptor complex, which plays a critical role in synaptic vesicle exocytosis. To date, six de novo SNAP25 mutations have been reported in patients with neurological features including seizures, intellectual disability, severe speech delay, and cerebellar ataxia. Here, we analyzed an Israeli family with two affected siblings showing seizures and cerebellar dysfunction by whole-exome sequencing, and identified a novel missense SNAP25 mutation (c.176G > C, p.Arg59Pro) inherited from their unaffected father. Two SNAP25 isoforms are known, SNAP25a and SNAP25b, which each contain a different exon 5. The c.176G > C mutation found in this study was specific to SNAP25b, while five previously reported mutations were identified in exons common to both isoforms. Another was previously reported to be specific to SNAP25b. Comparing clinical features of reported patients with SNAP25 mutations, the current patients demonstrated apparently milder clinical features with normal intelligence, and no magnetic resonance imaging abnormality or facial dysmorphism. Our results expand the clinical spectrum of SNAP25 mutations.

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We thank the members of the family for their participation in this study. We thank Irina Opincariu at Tel Aviv Medical Center for gathering clinical information. We also thank Sarah Williams, PhD, from Edanz Group ( for editing a draft of this manuscript. This work was supported by grants from Research on Measures for Intractable Diseases; Comprehensive Research on Disability Health and Welfare; the Strategic Research Program for Brain Science (SRPBS); the Practical Research Project for Rare/Intractable Diseases; the Initiative on Rare and Undiagnosed Diseases in Pediatrics; the Initiative on Rare and Undiagnosed Diseases in Adults from the Japan Agency for Medical Research and Development; a Grant-in-Aid for Scientific Research on Innovative Areas (Transcription Cycle) from the Ministry of Education, Culture, Sports, Science and Technology of Japan; Grants-in-Aid for Scientific Research (A and B); a Grant-in-Aid for Young Scientists (B); Challenging Exploratory Research from the Japan Society for the Promotion of Science; the fund for Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program in the Project for Developing Innovation Systems from the Japan Science and Technology Agency; and grants from the Ministry of Health, Labor and Welfare; and the Takeda Science Foundation.

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Correspondence to Naomichi Matsumoto.

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Fukuda, H., Imagawa, E., Hamanaka, K. et al. A novel missense SNAP25b mutation in two affected siblings from an Israeli family showing seizures and cerebellar ataxia. J Hum Genet 63, 673–676 (2018).

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