In Silico Structural Protein Evaluation of the Phenylalanine Hydroxylase p.(Tyr77His) Variant Associated with Benign Hyperphenylalaninemia as Identified through Mexican Newborn Screening
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patient Description
2.2. Biochemical Confirmatory Analysis
2.3. PAH Genotype Analysis
2.4. In Silico Protein Modeling, Docking, and Mutational Analyses of p.(Tyr77His) PAH Variant
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variant | c.229T>C or p.(Tyr77His) | c.1222C>T or p.(Arg408Trp) [rs5030858] |
---|---|---|
Variant type | Substitution | Substitution |
Coding effect | Missense | Missense |
Gene region | Exon 3 | Exon 12 |
Protein domain | Regulatory | Catalytic |
Enzyme activity | Unknown | 2% |
Allelic phenotype value (APV) | Unknown | 0 |
Worldwide allele frequency (gnomAD) [24] | Unknown | 0.0008910 |
ClinVar [25] | Uncertain significance (ID: RCV003316903.1) | Pathogenic (ID: 577) |
ACMG/AMP criteria for the interpretation of sequence variants [26,27] | Pathogenic IIIb (PS4, PM2, PM3, PP2, PP3, PP4) | Pathogenic IIb (PS3, PS4, PP1-S, PM1, PM2, PM3, PP1-M, PP1, PP2, PP3, PP4, PP5) |
First reported | Ohlsson, et al., 2016 [16] | DiLella, et al., 1987 [28] |
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Vela-Amieva, M.; Alcántara-Ortigoza, M.A.; González-del Angel, A.; Ibarra-González, I.; Fernández-Hernández, L.; Guillén-López, S.; López-Mejía, L.; Fernández-Lainez, C. In Silico Structural Protein Evaluation of the Phenylalanine Hydroxylase p.(Tyr77His) Variant Associated with Benign Hyperphenylalaninemia as Identified through Mexican Newborn Screening. Children 2023, 10, 1865. https://doi.org/10.3390/children10121865
Vela-Amieva M, Alcántara-Ortigoza MA, González-del Angel A, Ibarra-González I, Fernández-Hernández L, Guillén-López S, López-Mejía L, Fernández-Lainez C. In Silico Structural Protein Evaluation of the Phenylalanine Hydroxylase p.(Tyr77His) Variant Associated with Benign Hyperphenylalaninemia as Identified through Mexican Newborn Screening. Children. 2023; 10(12):1865. https://doi.org/10.3390/children10121865
Chicago/Turabian StyleVela-Amieva, Marcela, Miguel Angel Alcántara-Ortigoza, Ariadna González-del Angel, Isabel Ibarra-González, Liliana Fernández-Hernández, Sara Guillén-López, Lizbeth López-Mejía, and Cynthia Fernández-Lainez. 2023. "In Silico Structural Protein Evaluation of the Phenylalanine Hydroxylase p.(Tyr77His) Variant Associated with Benign Hyperphenylalaninemia as Identified through Mexican Newborn Screening" Children 10, no. 12: 1865. https://doi.org/10.3390/children10121865