المؤلفون: Olga Shchagina, Aysylu Murtazina, Polina Chausova, Mariya Orlova, Elena Dadali, Sergei Kurbatov, Sergey Kutsev, Aleksander Polyakov

المصدر: Frontiers in Genetics, Vol 15 (2024)

مصطلحات موضوعية: SH3TC2, CMT4C, mutation, neuropathy, Charcot-Marie-Tooth disease type 4C, hereditary motor and sensory neuropathy, Genetics, QH426-470

الوصف: Introduction:Charcot–Marie–Tooth disease type 4C (CMT4C) OMIM#601596 stands out as one of the most prevalent forms of recessive motor sensory neuropathy worldwide. This disorder results from biallelic pathogenic variants in the SH3TC2 gene.Methods:Within a cohort comprising 700 unrelated Russian patients diagnosed with Charcot–Marie–Tooth disease, we conducted a gene panel analysis encompassing 21 genes associated with hereditary neuropathies. Among the cohort, 394 individuals exhibited demyelinating motor and sensory neuropathy.Results and discussion:Notably, 10 cases of CMT4C were identified within this cohort. The prevalence of CMT4C among Russian demyelinating CMT patients lacking the PMP22 duplication is estimated at 2.5%, significantly differing from observations in European populations. In total, 4 novel and 9 previously reported variants in the SH3TC2 gene were identified. No accumulation of a major variant was detected. Three previously reported variants, c.2860C>T p. (Arg954*), p. (Arg658Cys) and c.279G>A p. (Lys93Lys), recurrently detected in unrelated families. Nucleotide alteration p. (Arg954*) is present in most of our patients (30%).

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fgene.2024.1381915/fullTest; https://doaj.org/toc/1664-8021Test

الوصول الحر: https://doaj.org/article/3d34053f980542aab2439eedeeee24e9Test

المؤلفون: Olga Shchagina, Mariya Orlova, Aisylu Murtazina, Alexandra Filatova, Mikhail Skoblov, Elena Dadali

المصدر: International Journal of Molecular Sciences, Vol 24, Iss 12, p 9786 (2023)

مصطلحات موضوعية: CMT, SH3TC2, MPZ, HMSN, gene panel, splicing variants, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: 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 SH3TC2 gene (c.279G>A and c.1177+5G>A), as well as a previously described variant c.449−9C>T in the MPZ 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 MPZ variant on splicing, but the c.1177+5G>A variant in the SH3TC2 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).

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/24/12/9786Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/5fb70464125c4a98a7c6301291a97dfbTest