Genetic Testing for a Patient with Suspected 3 Beta-Hydroxysteroid Dehydrogenase Deficiency: A Case of Unreported Genetic Variants
Abstract
:1. Introduction
2. Case Report
2.1. Patients, Clinical Presentation and Hormonal Analysis
2.1.1. Patient n.1
2.1.2. Patient n.2
3. Materials and Methods
3.1. Hormonal Testing
3.2. DNA Sequencing
3.3. In Silico Analysis
- Alamut v1.4 (http://www.interactive-biosoftware.com (accessed on 8 June 2022));
- Varsome 11.3 (https://varsome.com/ (accessed on 8 June 2022));
- Franklin by Geeox (https://help.genoox.com/en/collections/2077313-franklin-variant-interpretation (accessed on 8 June 2022)).
- MetaLR;
- REVEL;
- DEOGEN2;
- FATHMM;
- M-CAP;
- MVP;
- MutPred;
- Mutation assessor;
- PROVEAN;
- SIFT4G;
- PolyPhen2.
- SpliteSiteFinder;
- MaxEntScan;
- NNSPLICE;
- GeneSplicer.
4. Results
4.1. HSD3B2 c.370 A>G p.Ser124Gly
- Alamut: variant of uncertain significance (PM1, PM2, BP4);
- Varsome: variant of uncertain significance (PM2, PP3);
- Franklin: variant of uncertain significance, likely pathogenic (PM2, PM1 e PP2).
4.2. HSD3B2 c.308-6 G>A
- MaxEnt: −67.1%
- NNSPLICE: −0.9%
- SSF: −100.0%
5. Discussion
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Hormone | Patient n.1 Values | Patient n.2 Values | Normal Levels |
---|---|---|---|
17-OHP ng/mL | 86 | - | <10 (full term newborn)987654<2 (after 6 months) |
ACTH pg/mL | 250 | 53 | 8–53 |
Cortisol µg/L | 42 | 157 | 60–230 |
Aldosterone ng/mL | 514 | 197 | 70–550 |
PRA ng/mL/h | 2.07 | 12.8 | 1.31–3.95 |
Dihydrotestosterone pg/mL | 26 | - | 300–1200 |
Testosterone ng/mL | 1.3 | <0.2 | <0.4 |
Delta4androstenedione ng/mL | 18.5 | - | 0.60–5.60 |
DHEAS mcg/L | 1970 | 779 | 560–2360 |
LH U/L | 1.2 | - | <1.3 |
FSH U/L | 0.4 | - | <2 |
Na mEq/L | 136 | 139 | 136–146 |
K mEq/L | 5.3 | 4.6 | 3.5–5.3 |
Cl mEq/L | 105 | - | 97–110 |
Glucose | 64 | 78 | 70–110 |
Primer | Sequence |
---|---|
HSD3B2_1-2_FW | GCTCCAGTCCTTCCTCCAGG |
HSD3B2_1-2_REV | AGGTCAACCTCCCCACACCC |
HSD3B2_3_FW | GGATGTGTGACAATTCACTGC |
HSD3B2_3_REV | TCTTTCTGATCCTCATTTAACCAA |
HSD3B2_4_FW | CATGTGGTTGCAGCTCCTTT |
HSD3B2_4_REV | GAAGAAGACAGTAAGTTGGG |
HSD3B2_4INT_FW * | ACCTTGTACACTTGTGC |
HSD3B2_4INT_REV * | TGTGGCGGTTGAAGGG |
Predictor | Outcome |
---|---|
metal | Damaging (score: 0.8606) |
REVEL | Pathogenic (score: 0.6129) |
DEOGEN2 | Damaging (score: 0.6196, 0.7482) |
FATHMM | Damaging (score: −3.44) |
M-CAP | Damaging (score: 0.1732) |
MVP | Pathogenic (score: 0.9976) |
MutPred | Pathogenic (score: 0.935) |
Mutation assessor | High (score: 3.86) |
PROVEAN | Damaging (score: −3.02, −3.49) |
SIFT4G | Damaging (score: 0.002, 0.003) |
PolyPhen2 | HDivPred = probably damaging (score: 0.986)/HVarPred = possibly damaging (score: 0.898) |
EIGEN | Neutral (score −0.1586) |
LRT | Neutral (score 0.06347) |
Mutation taster | Polymorphism (score: 0.9774) |
PrimateAI | Tolerated (score 0.3522) |
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Menegatti, E.; Tessaris, D.; Barinotti, A.; Matarazzo, P.; Einaudi, S. Genetic Testing for a Patient with Suspected 3 Beta-Hydroxysteroid Dehydrogenase Deficiency: A Case of Unreported Genetic Variants. J. Clin. Med. 2022, 11, 5767. https://doi.org/10.3390/jcm11195767
Menegatti E, Tessaris D, Barinotti A, Matarazzo P, Einaudi S. Genetic Testing for a Patient with Suspected 3 Beta-Hydroxysteroid Dehydrogenase Deficiency: A Case of Unreported Genetic Variants. Journal of Clinical Medicine. 2022; 11(19):5767. https://doi.org/10.3390/jcm11195767
Chicago/Turabian StyleMenegatti, Elisa, Daniele Tessaris, Alice Barinotti, Patrizia Matarazzo, and Silvia Einaudi. 2022. "Genetic Testing for a Patient with Suspected 3 Beta-Hydroxysteroid Dehydrogenase Deficiency: A Case of Unreported Genetic Variants" Journal of Clinical Medicine 11, no. 19: 5767. https://doi.org/10.3390/jcm11195767