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

Hiroyuki Fukuda, Eri Imagawa, Kohei Hamanaka, Atsushi Fujita, Satomi Mitsuhashi, Satoko Miyatake, Takeshi Mizuguchi, Atsushi Takata, Noriko Miyake, Uri Kramer, Naomichi Matsumoto*, Aviva Fattal-Valevski

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)673-676
Number of pages4
JournalJournal of Human Genetics
Issue number5
StatePublished - 1 May 2018


FundersFunder number
Takeda Science Foundation
Japan Agency for Medical Research and Development
Japan Society for the Promotion of Science17H01539, 16H05357, 16H06254, 17K15630
Ministry of Education, Culture, Sports, Science and Technology
Japan Science and Technology Agency
Ministry of Health, Labour and Welfare


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