Asset Details
Do you wish to reserve the book?
X‐chromosomal inactivation patterns in women with Fabry disease
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
X‐chromosomal inactivation patterns in women with Fabry disease
Do you wish to request the book?
X‐chromosomal inactivation patterns in women with Fabry disease
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
X‐chromosomal inactivation patterns in women with Fabry disease
2022
Overview
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. X‐chromosomal inactivation patterns are of limited added value when diagnosing women with Fabry disease.
