Refine
Has Fulltext
- yes (23)
Is part of the Bibliography
- yes (23)
Year of publication
- 2024 (23) (remove)
Document Type
- Journal article (23) (remove)
Language
- English (23) (remove)
Keywords
- cell biology (2)
- ATF4 (1)
- C.376A>G (p.S126G) (1)
- Covid-19 (1)
- DCM genetic background (1)
- DNA double-strand breaks (1)
- DNA-encoded library synthesis (1)
- DNA-tagged amines (1)
- Drosophila (1)
- Fabry disease (1)
Institute
- Neurologische Klinik und Poliklinik (5)
- Institut für Organische Chemie (3)
- Theodor-Boveri-Institut für Biowissenschaften (3)
- Comprehensive Cancer Center Mainfranken (2)
- Deutsches Zentrum für Herzinsuffizienz (DZHI) (2)
- Institut für Klinische Biochemie und Pathobiochemie (2)
- Institut für Pharmakologie und Toxikologie (2)
- Institut für Pharmazie und Lebensmittelchemie (2)
- Institut für Psychologie (2)
- Klinik und Poliklinik für Anästhesiologie (ab 2004) (2)
- Medizinische Klinik und Poliklinik I (2)
- Rudolf-Virchow-Zentrum (2)
- Institut für Anatomie und Zellbiologie (1)
- Institut für Hygiene und Mikrobiologie (1)
- Institut für Klinische Neurobiologie (1)
- Institut für Medizinische Lehre und Ausbildungsforschung (1)
- Institut für Pädagogik (1)
- Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie (1)
- Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie (1)
- Klinik und Poliklinik für Nuklearmedizin (1)
- Medizinische Klinik und Poliklinik II (1)
- Pathologisches Institut (1)
Sonstige beteiligte Institutionen
Highlights
• The GLA variant S126G is not associated with Fabry symptoms in the presented case
• S126G has no effect on α-GAL A activity or Gb3 levels in this patient
• S126G sensory neurons show no electrophysiological abnormalities
Abstract
Fabry disease (FD) is a life-limiting disorder characterized by intracellular globotriaosylceramide (Gb3) accumulations. The underlying α-galactosidase A (α-GAL A) deficiency is caused by variants in the gene GLA. Variants of unknown significance (VUS) are frequently found in GLA and challenge clinical management. Here, we investigated a 49-year old man with cryptogenic lacunar cerebral stroke and the chance finding of the VUS S126G, who was sent to our center for diagnosis and initiation of a costly and life-long FD-specific treatment. We combined clinical examination with in vitro investigations of dermal fibroblasts (HDF), induced pluripotent stem cells (iPSC), and iPSC-derived sensory neurons. We analyzed α-GAL A activity in iPSC, Gb3 accumulation in all three cell types, and action potential firing in sensory neurons. Neurological examination and small nerve fiber assessment was normal except for reduced distal skin innervation. S126G iPSC showed normal α-GAL A activity compared to controls and no Gb3 deposits were found in all three cell types. Baseline electrophysiological characteristics of S126G neurons showed no difference compared to healthy controls as investigated by patch-clamp recordings. We pioneer multi-level cellular characterization of the VUS S126G using three cell types derived from a patient and provide further evidence for the benign nature of S126G in GLA, which is of great importance in the management of such cases in clinical practice.