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Case Reports
. 2020 Oct 22;11(11):1238.
doi: 10.3390/genes11111238.

Identification of a Novel de Novo Variant in the SYT2 Gene Causing a Rare Type of Distal Hereditary Motor Neuropathy

Olga Mironovich  1 , Elena Dadali  1 , Sergey Malmberg  2 , Tatyana Markova  1 , Oxana Ryzhkova  1 , Aleksander Poliakov  1
Affiliations
Case Reports

Identification of a Novel de Novo Variant in the SYT2 Gene Causing a Rare Type of Distal Hereditary Motor Neuropathy

Olga Mironovich et al. Genes (Basel). .

Abstract

Objective: To report the first de novo missense mutation in the SYT2 gene causing distal hereditary motor neuropathy.

Methods: Genetic testing was carried out, including clinical exome sequencing for the proband and Sanger sequencing for the proband and his parents. We described the clinical and electrophysiological features found in the patient.

Results: We reported a proband with a new de novo missense mutation, c.917C>T (p.Ser306Leu), in the C2B domain of SYT2. The clinical presentation was similar to that of phenotypes described in previous studies. A notable feature in our study was normal electrophysiological testing results of the patient.

Conclusions: In this study we reinforced the association between SYT2 mutations and distal hereditary motor neuropathy. We also described the clinical presentation of the patient carrying this pathogenic variant and provided unusual results of electrophysiological testing. The results showed that a diagnosis of SYT2-associated neuropathy should be based on the similarity of clinical manifestations, rather than the results of electrophysiological testing.

Keywords: SYT2 mutation; electrophysiological testing; first de novo mutation; hereditary motor neuropathy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Clinical presentation and genetic testing of the proband with a variant in the SYT2 gene: (a) The family tree showing the affected proband and unaffected parents and siblings; (b) Proband showing foot deformity and lower limb wasting; (c) Sanger sequencing results demonstrating the heterozygous c.917C>T missense SYT2 mutation in the proband; (d) Position of the c.917C>T mutation (red) in the SYT2 protein structure. This variant was highly conserved throughout different species. The cytoplasmic C2B domain of SYT2 is highlighted in blue.
Figure 2
Figure 2
Prediction model of the SYT2 protein: (a) with mutation Ser306Leu; (b) with mutation Asp307Ala; (c) with mutation Pro308Leu; wild type is highlighted with gray and blue; mutant is highlighted with red and dark red.
Figure 3
Figure 3
Test of rhythmic stimulation with tetanization (m. adductor pollicis ulnaris sin, C8 T1, 20 mA, duration—200 μs).
Figure 4
Figure 4
Motor unit potentials (MUPs) (m. tibialis anterior dex, peroneus, L4 L5 s1).
See this image and copyright information in PMC

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