TY  - JOUR
A1  - Lau, Kolja
A1  - Üçeyler, Nurcan
A1  - Cairns, Tereza
A1  - Lorenz, Lora
A1  - Sommer, Claudia
A1  - Schindehütte, Magnus
A1  - Amann, Kerstin
A1  - Wanner, Christoph
A1  - Nordbeck, Peter
T1  - Gene variants of unknown significance in Fabry disease: Clinical characteristics of c.376AG (p.Ser126Gly)
JF  - Molecular Genetics & Genomic Medicine
N2  - Background
Anderson–Fabry disease (FD) is an X-linked lysosomal storage disorder with varying organ involvement and symptoms, depending on the underlying mutation in the alpha-galactosidase A gene (HGNC: GLA). With genetic testing becoming more readily available, it is crucial to precisely evaluate pathogenicity of each genetic variant, in order to determine whether there is or might be not a need for FD-specific therapy in affected patients and relatives at the time point of presentation or in the future.

Methods
This case series investigates the clinical impact of the specific GLA gene variant c.376A>G (p.Ser126Gly) in five (one heterozygous and one homozygous female, three males) individuals from different families, who visited our center between 2009 and 2021. Comprehensive neurological, nephrological and cardiac examinations were performed in all cases. One patient received a follow-up examination after 12 years.

Results
Index events leading to suspicion of FD were mainly unspecific neurological symptoms. However, FD-specific biomarkers, imaging examinations (i.e., brain MRI, heart MRI), and tissue-specific diagnostics, including kidney and skin biopsies, did not reveal evidence for FD-specific symptoms or organ involvement but showed normal results in all cases. This includes findings from 12-year follow-up in one patient with renal biopsy.

Conclusion
These findings suggest that p.Ser126Gly represents a benign GLA gene variant which per se does not cause FD. Precise clinical evaluation in individuals diagnosed with genetic variations of unknown significance should be performed to distinguish common symptoms broadly prevalent in the general population from those secondary to FD.
KW  - diagnosis in Fabry disease
KW  - Fabry disease
KW  - gene variant
KW  - genotype/phenotype correlation
KW  - lysosomal storage disease
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312817
VL  - 10
IS  - 5
ER  - 
TY  - JOUR
A1  - Aster, Hans-Christoph
A1  - Evdokimov, Dimitar
A1  - Braun, Alexandra
A1  - Üçeyler, Nurcan
A1  - Kampf, Thomas
A1  - Pham, Mirko
A1  - Homola, György A.
A1  - Sommer, Claudia
T1  - CNS imaging characteristics in fibromyalgia patients with and without peripheral nerve involvement
JF  - Scientific Reports
N2  - We tested the hypothesis that reduced skin innervation in fibromyalgia syndrome is associated with specific CNS changes. This prospective case–control study included 43 women diagnosed with fibromyalgia syndrome and 40 healthy controls. We further compared the fibromyalgia subgroups with reduced (n = 21) and normal (n = 22) skin innervation. Brains were analysed for cortical volume, for white matter integrity, and for functional connectivity. Compared to controls, cortical thickness was decreased in regions of the frontal, temporal and parietal cortex in the fibromyalgia group as a whole, and decreased in the bilateral pericalcarine cortices in the fibromyalgia subgroup with reduced skin innervation. Diffusion tensor imaging revealed a significant increase in fractional anisotropy in the corona radiata, the corpus callosum, cingulum and fornix in patients with fibromyalgia compared to healthy controls and decreased FA in parts of the internal capsule and thalamic radiation in the subgroup with reduced skin innervation. Using resting-state fMRI, the fibromyalgia group as a whole showed functional hypoconnectivity between the right midfrontal gyrus and the posterior cerebellum and the right crus cerebellum, respectively. The subgroup with reduced skin innervation showed hyperconnectivity between the inferior frontal gyrus, the angular gyrus and the posterior parietal gyrus. Our results suggest that the subgroup of fibromyalgia patients with pronounced pathology in the peripheral nervous system shows alterations in morphology, structural and functional connectivity also at the level of the encephalon. We propose considering these subgroups when conducting clinical trials.
KW  - fibromyalgia syndrome
KW  - CNS imaging
KW  - peripheral nerve involvement
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300562
VL  - 12
IS  - 1
ER  -