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

Journal of Human Genetics
Hiroyuki FukudaAviva Fattal-Valevski

Abstract

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.

References

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Citations

May 8, 2020·Journal of Neurochemistry·Katherine BonnycastleMichael A Cousin
Sep 23, 2020·Journal of Cellular Physiology·Bor L Tang
Sep 12, 2020·Journal of Neurochemistry·Holly MellandSarah L Gordon
Aug 2, 2020·Journal of Neurochemistry·Abinayah JohnKate Baker
Jan 8, 2021·Neuron·Roman PraschbergerPatrik Verstreken
Dec 11, 2020·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Chiara KlöcknerKonrad Platzer

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Methods Mentioned

BETA
PCR
Exome Sequencing

Software Mentioned

MutationTaster
SIFT
Miseq
Polyphen2

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