Hyperphenylalaninemias genotyping: Results of over 60 years of history in Lombardy, Italy
Abstract Background Hyperphenylalaninemias (HPA) are due to several gene mutations, of which the PAH gene is the most frequently involved. Prevalence and incidence of disease vary between populations, with genotype/phenotype correlations not always capable to correctly predict disease severity. The...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-03-01
|
| Series: | Endocrinology, Diabetes & Metabolism |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/edm2.396 |
| _version_ | 1811154989031096320 |
|---|---|
| author | Valentina Rovelli Graziella Cefalo Vittoria Ercoli Juri Zuvadelli Turri Olivia Daniela Graziani Alberti Luisella Davide Bassi Alice Re Dionigi Raed Selmi Sabrina Paci Elisabetta Salvatici Giuseppe Banderali |
| author_facet | Valentina Rovelli Graziella Cefalo Vittoria Ercoli Juri Zuvadelli Turri Olivia Daniela Graziani Alberti Luisella Davide Bassi Alice Re Dionigi Raed Selmi Sabrina Paci Elisabetta Salvatici Giuseppe Banderali |
| author_sort | Valentina Rovelli |
| collection | DOAJ |
| description | Abstract Background Hyperphenylalaninemias (HPA) are due to several gene mutations, of which the PAH gene is the most frequently involved. Prevalence and incidence of disease vary between populations, with genotype/phenotype correlations not always capable to correctly predict disease severity. The aim of this study was to give an overview of PAH mutations among one of the largest cohort of patients among Europe, born in Lombardy (Italy) starting from late 1970 s and including over a 60 years of activity; furthermore, to evaluate and discuss identified genotype/phenotype correlations and related reliability. Patients/Methods Eight hundred and twenty‐six HPA patients in current follow‐up at the San Paolo Hospital in Milan (Italy) were retrospectively reviewed, including molecular results and allelic phenotype and genotype values (attributed on the basis of the APV/GPV system) to verify genotype–phenotype correlations. Results A total of 166 different PAH variants were reviewed; of those, seven variants were identified as not previously described in literature. Most frequently reported variant was p.Ala403Val, followed by p.Arg261Gln, p.Val245Ala, IVS10‐11 g>a, p.Tyr414Cys and p.Leu48Ser. Phenotype prediction, based on APV/GPV, matched the actual phenotype in most cases, but not always. Conclusion/Discussion The cohort of patients included in this study constitute a representative sample of the HPA population worldwide. Studies on this sample may allow to improve clinical and genetic evaluation performances for affected patients, consequently to develop personalized medicine interventions and provide more precise indications on the correct treatment approach based on the accumulated evidence, also in light of a prognostically reliable but not always conclusive APV/GPV system. |
| first_indexed | 2024-04-10T04:26:35Z |
| format | Article |
| id | doaj.art-b8f12589c5bd4c2cba0716180c4abc04 |
| institution | Directory Open Access Journal |
| issn | 2398-9238 |
| language | English |
| last_indexed | 2024-04-10T04:26:35Z |
| publishDate | 2023-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Endocrinology, Diabetes & Metabolism |
| spelling | doaj.art-b8f12589c5bd4c2cba0716180c4abc042023-03-10T14:33:26ZengWileyEndocrinology, Diabetes & Metabolism2398-92382023-03-0162n/an/a10.1002/edm2.396Hyperphenylalaninemias genotyping: Results of over 60 years of history in Lombardy, ItalyValentina Rovelli0Graziella Cefalo1Vittoria Ercoli2Juri Zuvadelli3Turri Olivia4Daniela Graziani5Alberti Luisella6Davide Bassi7Alice Re Dionigi8Raed Selmi9Sabrina Paci10Elisabetta Salvatici11Giuseppe Banderali12Clinical Department of Pediatrics, Inborn Errors of Metabolism Unit, San Paolo Hospital, ASST Santi Paolo e Carlo University of Milan Milan ItalyClinical Department of Pediatrics, Inborn Errors of Metabolism Unit, San Paolo Hospital, ASST Santi Paolo e Carlo University of Milan Milan ItalyClinical Department of Pediatrics, Inborn Errors of Metabolism Unit, San Paolo Hospital, ASST Santi Paolo e Carlo University of Milan Milan ItalyClinical Department of Pediatrics, Inborn Errors of Metabolism Unit, San Paolo Hospital, ASST Santi Paolo e Carlo University of Milan Milan ItalyDepartment of Laboratory Diagnostic Technologies San Paolo Hospital, ASST Santi Paolo e Carlo Milan ItalyDepartment of Laboratory Diagnostic Technologies San Paolo Hospital, ASST Santi Paolo e Carlo Milan ItalyRegional Laboratory of Newborn Screening, Department of Women, Mothers and Neonatal Care, Children's Hospital “V. Buzzi” ASST Fatebenefratelli Sacco Milan ItalyClinical Department of Pediatrics, Inborn Errors of Metabolism Unit, San Paolo Hospital, ASST Santi Paolo e Carlo University of Milan Milan ItalyClinical Department of Pediatrics, Inborn Errors of Metabolism Unit, San Paolo Hospital, ASST Santi Paolo e Carlo University of Milan Milan ItalyClinical Department of Pediatrics, Inborn Errors of Metabolism Unit, San Paolo Hospital, ASST Santi Paolo e Carlo University of Milan Milan ItalyClinical Department of Pediatrics, Inborn Errors of Metabolism Unit, San Paolo Hospital, ASST Santi Paolo e Carlo University of Milan Milan ItalyClinical Department of Pediatrics, Inborn Errors of Metabolism Unit, San Paolo Hospital, ASST Santi Paolo e Carlo University of Milan Milan ItalyClinical Department of Pediatrics, Inborn Errors of Metabolism Unit, San Paolo Hospital, ASST Santi Paolo e Carlo University of Milan Milan ItalyAbstract Background Hyperphenylalaninemias (HPA) are due to several gene mutations, of which the PAH gene is the most frequently involved. Prevalence and incidence of disease vary between populations, with genotype/phenotype correlations not always capable to correctly predict disease severity. The aim of this study was to give an overview of PAH mutations among one of the largest cohort of patients among Europe, born in Lombardy (Italy) starting from late 1970 s and including over a 60 years of activity; furthermore, to evaluate and discuss identified genotype/phenotype correlations and related reliability. Patients/Methods Eight hundred and twenty‐six HPA patients in current follow‐up at the San Paolo Hospital in Milan (Italy) were retrospectively reviewed, including molecular results and allelic phenotype and genotype values (attributed on the basis of the APV/GPV system) to verify genotype–phenotype correlations. Results A total of 166 different PAH variants were reviewed; of those, seven variants were identified as not previously described in literature. Most frequently reported variant was p.Ala403Val, followed by p.Arg261Gln, p.Val245Ala, IVS10‐11 g>a, p.Tyr414Cys and p.Leu48Ser. Phenotype prediction, based on APV/GPV, matched the actual phenotype in most cases, but not always. Conclusion/Discussion The cohort of patients included in this study constitute a representative sample of the HPA population worldwide. Studies on this sample may allow to improve clinical and genetic evaluation performances for affected patients, consequently to develop personalized medicine interventions and provide more precise indications on the correct treatment approach based on the accumulated evidence, also in light of a prognostically reliable but not always conclusive APV/GPV system.https://doi.org/10.1002/edm2.396genotypehyperphenylalaninemiaPAHphenotypephenylketonuriaPKU |
| spellingShingle | Valentina Rovelli Graziella Cefalo Vittoria Ercoli Juri Zuvadelli Turri Olivia Daniela Graziani Alberti Luisella Davide Bassi Alice Re Dionigi Raed Selmi Sabrina Paci Elisabetta Salvatici Giuseppe Banderali Hyperphenylalaninemias genotyping: Results of over 60 years of history in Lombardy, Italy Endocrinology, Diabetes & Metabolism genotype hyperphenylalaninemia PAH phenotype phenylketonuria PKU |
| title | Hyperphenylalaninemias genotyping: Results of over 60 years of history in Lombardy, Italy |
| title_full | Hyperphenylalaninemias genotyping: Results of over 60 years of history in Lombardy, Italy |
| title_fullStr | Hyperphenylalaninemias genotyping: Results of over 60 years of history in Lombardy, Italy |
| title_full_unstemmed | Hyperphenylalaninemias genotyping: Results of over 60 years of history in Lombardy, Italy |
| title_short | Hyperphenylalaninemias genotyping: Results of over 60 years of history in Lombardy, Italy |
| title_sort | hyperphenylalaninemias genotyping results of over 60 years of history in lombardy italy |
| topic | genotype hyperphenylalaninemia PAH phenotype phenylketonuria PKU |
| url | https://doi.org/10.1002/edm2.396 |
| work_keys_str_mv | AT valentinarovelli hyperphenylalaninemiasgenotypingresultsofover60yearsofhistoryinlombardyitaly AT graziellacefalo hyperphenylalaninemiasgenotypingresultsofover60yearsofhistoryinlombardyitaly AT vittoriaercoli hyperphenylalaninemiasgenotypingresultsofover60yearsofhistoryinlombardyitaly AT jurizuvadelli hyperphenylalaninemiasgenotypingresultsofover60yearsofhistoryinlombardyitaly AT turriolivia hyperphenylalaninemiasgenotypingresultsofover60yearsofhistoryinlombardyitaly AT danielagraziani hyperphenylalaninemiasgenotypingresultsofover60yearsofhistoryinlombardyitaly AT albertiluisella hyperphenylalaninemiasgenotypingresultsofover60yearsofhistoryinlombardyitaly AT davidebassi hyperphenylalaninemiasgenotypingresultsofover60yearsofhistoryinlombardyitaly AT aliceredionigi hyperphenylalaninemiasgenotypingresultsofover60yearsofhistoryinlombardyitaly AT raedselmi hyperphenylalaninemiasgenotypingresultsofover60yearsofhistoryinlombardyitaly AT sabrinapaci hyperphenylalaninemiasgenotypingresultsofover60yearsofhistoryinlombardyitaly AT elisabettasalvatici hyperphenylalaninemiasgenotypingresultsofover60yearsofhistoryinlombardyitaly AT giuseppebanderali hyperphenylalaninemiasgenotypingresultsofover60yearsofhistoryinlombardyitaly |