دورية أكاديمية
The Global ALPL gene variant classification project: Dedicated to deciphering variants.
| العنوان: | The Global ALPL gene variant classification project: Dedicated to deciphering variants. |
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| المؤلفون: | Farman MR; Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz, Linz, Austria., Rehder C; Duke University Medical Center, Department of Pathology, Durham, USA., Malli T; Laboratory for Molecular Genetic Diagnostics, Ordensklinikum Linz, Linz, Austria., Rockman-Greenberg C; Department of Pediatrics and Child Health Max Rady College of Medicine, Rady Faculty of Health Sciences, Winnipeg, Canada., Dahir K; Vanderbilt University Medical Center, Program for Metabolic Bone Disorders, Nashville, TN, USA., Martos-Moreno GÁ; Departments of Pediatrics & Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain; Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain; CIBER Fisiopatología de la Obesidad y Nutrición, ISCIII, Madrid, Spain, Linglart A; AP-HP, Paris Saclay University, INSERM, Bicêtre Paris Saclay hospital, Le Kremlin-Bicêtre, France, Ozono K; Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan, Seefried L; Julius-Maximilian University, Würzburg, Germany., Del Angel G; Alexion, AstraZeneca Rare Disease, Boston, MA, USA, Webersinke G; Laboratory for Molecular Genetic Diagnostics, Ordensklinikum Linz, Linz, Austria., Barbazza F; Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz, Linz, Austria., John LK; Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz, Linz, Austria., Delana Mudiyanselage SMA; Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz, Linz, Austria., Högler F; Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz, Linz, Austria., Nading EB; Duke University Medical Center, Division of Medical Genetics, Department of Pediatrics, Durham, USA, Huggins E; Duke University Medical Center, Division of Medical Genetics, Department of Pediatrics, Durham, USA, Rush ET; Division of Clinical Genetics, Children's Mercy Hospital Kansas City, Kansas City, MO, USA; Department of Internal Medicine, University of Kansas School of Medicine, Kansas City, KS, USA; Department of Pediatrics, University of Missouri – Kansas City School of Medicine, Kansas City, MO, USA, El-Gazzar A; Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz, Linz, Austria., Kishnani PS; Duke University Medical Center, Division of Medical Genetics, Department of Pediatrics, Durham, USA, Högler W; Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz, Linz, Austria. |
| المصدر: | Bone [Bone] 2024 Jan; Vol. 178, pp. 116947. Date of Electronic Publication: 2023 Oct 26. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: United States NLM ID: 8504048 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2763 (Electronic) Linking ISSN: 18732763 NLM ISO Abbreviation: Bone Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: New York : Elsevier Science Original Publication: Elmsford, NY : Pergamon Press, c1985- |
| مواضيع طبية MeSH: | Alkaline Phosphatase*/genetics , Alkaline Phosphatase*/chemistry , Hypophosphatasia*/genetics , Hypophosphatasia*/pathology, Humans ; Mutation/genetics ; Artificial Intelligence ; Delayed Diagnosis |
| مستخلص: | Background: Hypophosphatasia (HPP) is an inherited multisystem disorder predominantly affecting the mineralization of bones and teeth. HPP is caused by pathogenic variants in ALPL, which encodes tissue non-specific alkaline phosphatase (TNSALP). Variants of uncertain significance (VUS) cause diagnostic delay and uncertainty amongst patients and health care providers. Results: The ALPL gene variant database (https://alplmutationdatabase.jku.at/) is an open-access archive for interpretation of the clinical significance of variants reported in ALPL. The database contains coding and non-coding variants, including single nucleotide variants, insertions/deletions and structural variants affecting coding or non-coding sequences of ALPL. Each variant in the database is displayed with details explaining the corresponding pathogenicity, and all reported genotypes and phenotypes, including references. In 2021, the ALPL gene variant classification project was established to reclassify VUS and continuously assess and update genetic, phenotypic, and functional variant information in the database. For this purpose, the database provides a unique submission system for clinicians, geneticists, genetic counselors, and researchers to submit VUS within ALPL for classification. An international, multidisciplinary consortium of HPP experts has been established to reclassify the submitted VUS using a multi-step process adhering to the stringent ACMG/AMP variant classification guidelines. These steps include a clinical phenotype assessment, deep literature research including artificial intelligence technology, molecular genetic assessment, and in-vitro functional testing of variants in a co-transfection model to measure ALP residual activity. Conclusion: This classification project and the ALPL gene variant database will serve the global medical community, widen the genotypic and phenotypic HPP spectrum by reporting and characterizing new ALPL variants based on ACMG/AMP criteria and thus facilitate improved genetic counseling and medical decision-making for affected patients and families. The project may also serve as a gold standard framework for multidisciplinary collaboration for variant interpretation in other rare diseases. Competing Interests: Declaration of competing interest The authors declare that they have no competing interests. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: ACMG; Alkaline phosphatase; Hypophosphatasia; Reclassification; Vitamin B6 |
| المشرفين على المادة: | EC 3.1.3.1 (Alkaline Phosphatase) EC 3.1.3.1 (ALPL protein, human) |
| تواريخ الأحداث: | Date Created: 20231028 Date Completed: 20231127 Latest Revision: 20240304 |
| رمز التحديث: | 20240305 |
| DOI: | 10.1016/j.bone.2023.116947 |
| PMID: | 37898381 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1873-2763 |
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| DOI: | 10.1016/j.bone.2023.116947 |