X-chromosomal inactivation patterns in women with Fabry disease
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-312795
- Background Although Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene (GLA), women may develop severe symptoms. We investigated X-chromosomal inactivation patterns (XCI) as a potential determinant of symptom severity in FD women. Patients and Methods We included 95 women with mutations in GLA (n = 18 with variants of unknown pathogenicity) and 50 related men, and collected mouth epithelial cells, venous blood, and skin fibroblasts for XCI analysis using the methylation statusBackground Although Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene (GLA), women may develop severe symptoms. We investigated X-chromosomal inactivation patterns (XCI) as a potential determinant of symptom severity in FD women. Patients and Methods We included 95 women with mutations in GLA (n = 18 with variants of unknown pathogenicity) and 50 related men, and collected mouth epithelial cells, venous blood, and skin fibroblasts for XCI analysis using the methylation status of the androgen receptor gene. The mutated X-chromosome was identified by comparison of samples from relatives. Patients underwent genotype categorization and deep clinical phenotyping of symptom severity. Results 43/95 (45%) women carried mutations categorized as classic. The XCI pattern was skewed (i.e., ≥75:25% distribution) in 6/87 (7%) mouth epithelial cell samples, 31/88 (35%) blood samples, and 9/27 (33%) skin fibroblast samples. Clinical phenotype, α-galactosidase A (GAL) activity, and lyso-Gb3 levels did not show intergroup differences when stratified for X-chromosomal skewing and activity status of the mutated X-chromosome. Conclusions X-inactivation patterns alone do not reliably reflect the clinical phenotype of women with FD when investigated in biomaterial not directly affected by FD. However, while XCI patterns may vary between tissues, blood frequently shows skewing of XCI patterns.…
Autor(en): | Laura Wagenhäuser, Vanessa Rickert, Claudia Sommer, Christoph Wanner, Peter Nordbeck, Simone Rost, Nurcan Üçeyler |
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URN: | urn:nbn:de:bvb:20-opus-312795 |
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): | Molecular Genetics & Genomic Medicine |
Erscheinungsjahr: | 2022 |
Band / Jahrgang: | 10 |
Heft / Ausgabe: | 9 |
Aufsatznummer: | e2029 |
Originalveröffentlichung / Quelle: | Molecular Genetics & Genomic Medicine (2022) 10:9, e2029. doi:10.1002/mgg3.2029 |
DOI: | https://doi.org/10.1002/mgg3.2029 |
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; X-chromosomal inactivation; female Fabry patients |
Datum der Freischaltung: | 24.04.2023 |
Open-Access-Publikationsfonds / Förderzeitraum 2022 | |
Lizenz (Deutsch): | CC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International |