Stratification of Fabry mutations in clinical practice: a closer look at α‐galactosidase A‐3D structure
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-218125
- Background Fabry disease (FD) is an X‐linked lysosomal storage and multi‐system disorder due to mutations in the α‐galactosidase A (α‐GalA) gene. We investigated the impact of individual amino acid exchanges in the α‐GalA 3D‐structure on the clinical phenotype of FD patients. Patients and methods We enrolled 80 adult FD patients with α‐GalA missense mutations and stratified them into three groups based on the amino acid exchange location in the α‐GalA 3D‐structure: patients with active site mutations, buried mutations and other mutations.Background Fabry disease (FD) is an X‐linked lysosomal storage and multi‐system disorder due to mutations in the α‐galactosidase A (α‐GalA) gene. We investigated the impact of individual amino acid exchanges in the α‐GalA 3D‐structure on the clinical phenotype of FD patients. Patients and methods We enrolled 80 adult FD patients with α‐GalA missense mutations and stratified them into three groups based on the amino acid exchange location in the α‐GalA 3D‐structure: patients with active site mutations, buried mutations and other mutations. Patient subgroups were deep phenotyped for clinical and laboratory parameters and FD‐specific treatment. Results Patients with active site or buried mutations showed a severe phenotype with multi‐organ involvement and early disease manifestation. Patients with other mutations had a milder phenotype with less organ impairment and later disease onset. α‐GalA activity was lower in patients with active site or buried mutations than in those with other mutations (P < 0.01 in men; P < 0.05 in women) whilst lyso‐Gb3 levels were higher (P < 0.01 in men; <0.05 in women). Conclusions The type of amino acid exchange location in the α‐GalA 3D‐structure determines disease severity and temporal course of symptom onset. Patient stratification using this parameter may become a useful tool in the management of FD patients.…
Autor(en): | V. Rickert, L. Wagenhäuser, P. Nordbeck, C. Wanner, C. Sommer, S. Rost, N. Üçeyler |
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URN: | urn:nbn:de:bvb:20-opus-218125 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Institut für Humangenetik |
Medizinische Fakultät / Neurologische Klinik und Poliklinik | |
Medizinische Fakultät / Medizinische Klinik und Poliklinik I | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Journal of Internal Medicine |
Erscheinungsjahr: | 2020 |
Band / Jahrgang: | 288 |
Heft / Ausgabe: | 5 |
Erste Seite: | 593 |
Letzte Seite: | 604 |
Originalveröffentlichung / Quelle: | Journal of Internal Medicine 2020, 288(5):593-604. DOI: 10.1111/joim.13125 |
DOI: | https://doi.org/10.1111/joim.13125 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | Fabry disease; Fabry genotype; Fabry phenotype; lyso‐Gb3; α‐GalA 3D‐structure |
Datum der Freischaltung: | 20.08.2021 |
Lizenz (Deutsch): | CC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International |