Evaluation of Pathogenicity and Causativity of Variants in the <i>MPZ</i> and <i>SH3TC2</i> Genes in a Family Case of Hereditary Peripheral Neuropathy
The implementation of NGS methods into clinical practice allowed researchers effectively to establish the molecular cause of a disorder in cases of a genetically heterogeneous pathology. In cases of several potentially causative variants, we need additional analysis that can help in choosing a prope...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/12/9786 |
| Summary: | The implementation of NGS methods into clinical practice allowed researchers effectively to establish the molecular cause of a disorder in cases of a genetically heterogeneous pathology. In cases of several potentially causative variants, we need additional analysis that can help in choosing a proper causative variant. In the current study, we described a family case of hereditary motor and sensory neuropathy (HMSN) type 1 (Charcot–Marie–Tooth disease). DNA analysis revealed two variants in the <i>SH3TC2</i> gene (c.279G>A and c.1177+5G>A), as well as a previously described variant c.449−9C>T in the <i>MPZ</i> gene, in a heterozygous state. This family segregation study was incomplete because of the proband’s father's unavailability. To evaluate the variants’ pathogenicity, minigene splicing assay was carried out. This study showed no effect of the <i>MPZ</i> variant on splicing, but the c.1177+5G>A variant in the <i>SH3TC2</i> gene leads to the retention of 122 nucleotides from intron 10 in the RNA sequence, causing a frameshift and an occurrence of a premature stop codon (NP_078853.2:p.Ala393GlyfsTer2). |
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| ISSN: | 1661-6596 1422-0067 |