TY  - JOUR
A1  - Wagenhäuser, Laura
A1  - Rickert, Vanessa
A1  - Sommer, Claudia
A1  - Wanner, Christoph
A1  - Nordbeck, Peter
A1  - Rost, Simone
A1  - Üçeyler, Nurcan
T1  - X-chromosomal inactivation patterns in women with Fabry disease
T2  - Molecular Genetics & Genomic Medicine
N2  - 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 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.
KW  - Fabry disease
KW  - Fabry genotype
KW  - Fabry phenotype
KW  - female Fabry patients
KW  - X-chromosomal inactivation
Y1  - 2022
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/31279
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-312795
VL  - 10
IS  - 9
ER  -