Using Precision Medicine to Disentangle Genotype–Phenotype Relationships in Twins with Rett Syndrome: A Case Report
Abstract
:1. Introduction
2. Methods
2.1. Subject Demographics
2.2. Buspirone Administration (Twin A)
2.3. Evaluation of Clinical Severity in Twin A and B
2.4. Measurement of Heart Rate Variability Parameters
2.4.1. Autonomic Heart Rate Variability Parameters
2.4.2. Measurement of Autonomic HRV Parameters
2.5. Targeted Genotyping
2.5.1. Sample Collection
2.5.2. Targeted Genotype Reporting
2.5.3. MECP2
2.5.4. BDNF
2.6. Statistical Analyses
2.7. Informed Consent and Ethics
3. Results
3.1. Longitudinal Monitoring of Clinical Severity and Symptom Frequency
3.1.1. Initiation of Buspirone (Twin A)
3.1.2. Bayesian Inferential Methods: Frequentist Significance Test
3.2. Longitudinal Assessment of HRV Parameters
3.2.1. After Initiation of Buspirone (Twin A)
3.2.2. Non-Parametric Wilcoxon Signed-Rank Tests
3.3. MECP2 and BDNF Genotyping
3.3.1. MECP2
3.3.2. BDNF
4. Discussion
5. Conclusions
6. Limitations
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Twin A | Twin B | ||||
---|---|---|---|---|---|
Metric | Epoch | Awake | Sleep | Awake | Sleep |
Mean (bpm) HR (min; max) | 01/2022 | 119 (38; 175) | 133 (70; 160) | 130 (67; 175) | 129 (82; 175) |
12/2022 | 125 (59; 160) | 128 (72; 167) | 126 (57; 175) | 131 (98; 160) | |
pNN50 (%) | 01/2022 | 3.33 | 0.18 | 3.34 | 0.534 |
12/2022 | 11.89 | 1.24 | 1.48 | 0.1 | |
SDNN (ms) | 01/2022 | 29.9 | 12.05 | 42.19 | 21.74 |
12/2022 | 39.41 | 21.28 | 42.24 | 24.35 | |
RMSSD (ms) | 01/2022 | 28.76 | 16.61 | 25.89 | 17.91 |
12/2022 | 44.44 | 19.60 | 25.77 | 13.39 |
MECP2 | BDNF | |||
---|---|---|---|---|
Genotype * | Phenotype | Genotype | Phenotype | |
Twin A | Heterozygous c.1160_*5215del p(Pro387_Ser486delinsGln) | Pathogenic | 434C>T C/T (heterozygous for rs6265 T Allele) | Associated with reduced activity-dependent secretion of BDNF from neurons and impaired BDNF signalling |
Twin B | Heterozygous c.1160_*5215del p(Pro387_Ser486delinsGln) | Pathogenic | 434C>T C/C (homozygous for rs6265 C Allele) | Associated with normal activity-dependent secretion of BDNF from neurons and normal BDNF signalling |
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Singh, J.; Wilkins, G.; Goodman-Vincent, E.; Chishti, S.; Bonilla Guerrero, R.; Fiori, F.; Ameenpur, S.; McFadden, L.; Zahavi, Z.; Santosh, P. Using Precision Medicine to Disentangle Genotype–Phenotype Relationships in Twins with Rett Syndrome: A Case Report. Curr. Issues Mol. Biol. 2024, 46, 8424-8440. https://doi.org/10.3390/cimb46080497
Singh J, Wilkins G, Goodman-Vincent E, Chishti S, Bonilla Guerrero R, Fiori F, Ameenpur S, McFadden L, Zahavi Z, Santosh P. Using Precision Medicine to Disentangle Genotype–Phenotype Relationships in Twins with Rett Syndrome: A Case Report. Current Issues in Molecular Biology. 2024; 46(8):8424-8440. https://doi.org/10.3390/cimb46080497
Chicago/Turabian StyleSingh, Jatinder, Georgina Wilkins, Ella Goodman-Vincent, Samiya Chishti, Ruben Bonilla Guerrero, Federico Fiori, Shashidhar Ameenpur, Leighton McFadden, Zvi Zahavi, and Paramala Santosh. 2024. "Using Precision Medicine to Disentangle Genotype–Phenotype Relationships in Twins with Rett Syndrome: A Case Report" Current Issues in Molecular Biology 46, no. 8: 8424-8440. https://doi.org/10.3390/cimb46080497