Identification of a Novel Missense Mutation of POLR3A Gene in a Cohort of Sicilian Patients with Leukodystrophy
Abstract
:1. Introduction
2. Materials and Methods
2.1. DNA Preparation
2.2. Genotypic Identification by NGS Sequencing
2.3. Sanger Sequencing
3. Results
3.1. Study Subjects
3.2. Phenotypic Features of the Analyzed Subject
3.3. Identification of the Missense Mutation in the POLR3A (NM_007055.3) Gene
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Sample | Age | Gender | Brain Magnetic Resonance Imaging (MRI) | NGS Results |
---|---|---|---|---|
4041-NP1139 | 31 | F | Diffuse hypomyelination of the subcortical and deep white matter, enlarged high convexity CSF spaces, ponto-cerebellar hypoplasia, and thin corpus callosum. | Causative mutations |
5078-NP1688 | 23 | M | Slight peri- and supra-ventricular white matter hyperintensities and cortical atrophy. | Causative mutations |
3277-CS130A | 40 | F | Diffuse hyperintensities in the corona radiata and centra semiovale. | Negative |
3809-VR103A | 26 | F | Slight and diffuse signal alteration in the subcortical and deep white matter, and thin corpus callosum. | Negative |
5303-VR813A | 24 | F | Large and irregular hyperintensities in the subcortical and perventricular with matter on T2-weighed and FLAIR sequences. | Negative |
Sample | Gene | Function | Genotype | Codon | Protein | Coding | HGMD a | ACMG b | Refs. |
---|---|---|---|---|---|---|---|---|---|
4041-NP1139 | POLR3A | Missense | C/T | AGT | p.Gly1240Ser | c.3718G>A | Yes | L.P. | [10,11] |
POLR3A | Missense | G/T | AAG | p.Gln599Lys | c.1795C>A | Yes | L.P. | [10] | |
5078-NP1688 | POLR3A | Missense | G/T | AAG | p.Gln599Lys | c.1795C>A | Yes | L.P. | [10] |
POLR3A | Missense | T/C | GAA | p.Lys110Glu | c.328A>G | - | L.P. | (c) |
In Silico Predictive Tool | Prediction/Score/PHRED-Scaled |
---|---|
CADD_pred | 27.2 (>30 highly pathogenic; >20 pathogenic) |
DANN_score | 0.999 (range from 0 to 1) * |
FATHMM_pred | Tolerated |
GERP++_RS | 5.67 (range from −12.3 to 6.17) * |
LRT_pred | Deleterious |
M-CAP_pred | Damaging |
MetaSVM_pred | Tolerated |
MetaLR_pred | Tolerated |
MutationAssessor_pred | Medium |
MutationTaster_pred | Damaging |
PROVEAN_pred | Deleterious |
Polyphen2_HDIV_pred | Probably damaging |
SIFT_pred | Deleterious |
SiPhy_29way_logOdds | 15.915 (range from 0 to 37.9718) * |
Fathmm-MKL_coding_pred | Damaging |
ACMG criteria | Likely Pathogenic ** |
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Musumeci, A.; Calì, F.; Scuderi, C.; Vinci, M.; Vitello, G.A.; Musumeci, S.A.; Chiavetta, V.; Federico, C.; Amore, G.; Saccone, S.; et al. Identification of a Novel Missense Mutation of POLR3A Gene in a Cohort of Sicilian Patients with Leukodystrophy. Biomedicines 2022, 10, 2276. https://doi.org/10.3390/biomedicines10092276
Musumeci A, Calì F, Scuderi C, Vinci M, Vitello GA, Musumeci SA, Chiavetta V, Federico C, Amore G, Saccone S, et al. Identification of a Novel Missense Mutation of POLR3A Gene in a Cohort of Sicilian Patients with Leukodystrophy. Biomedicines. 2022; 10(9):2276. https://doi.org/10.3390/biomedicines10092276
Chicago/Turabian StyleMusumeci, Antonino, Francesco Calì, Carmela Scuderi, Mirella Vinci, Girolamo Aurelio Vitello, Sebastiano Antonino Musumeci, Valeria Chiavetta, Concetta Federico, Greta Amore, Salvatore Saccone, and et al. 2022. "Identification of a Novel Missense Mutation of POLR3A Gene in a Cohort of Sicilian Patients with Leukodystrophy" Biomedicines 10, no. 9: 2276. https://doi.org/10.3390/biomedicines10092276
APA StyleMusumeci, A., Calì, F., Scuderi, C., Vinci, M., Vitello, G. A., Musumeci, S. A., Chiavetta, V., Federico, C., Amore, G., Saccone, S., Di Rosa, G., & Nicotera, A. G. (2022). Identification of a Novel Missense Mutation of POLR3A Gene in a Cohort of Sicilian Patients with Leukodystrophy. Biomedicines, 10(9), 2276. https://doi.org/10.3390/biomedicines10092276