Clinical Medicine I. (Poster discussion will take place in the Aula during the Coffee Break)
Tamás Szlepák1, Robert Sepp2, Eva Rakoczi3, Krisztina Nemeth4, Tamas Gyimesi5, Sandor
Molnar6, Gyorgy Fekete4, Maria Judit Molnár1
1Semmelweis University, Institute of Genomic Medicine and Rare Disorders, Budapest
2University of Szeged, Second Department of Internal Medicine and Cardiology
3University of Debrecen, Department of Rheumatology, Debrecen
4Semmelweis University, 2nd Department of Paediatrics, Budapest
5University of Pécs, 2nd Department of Internal Medicine and Nephrological Center, Pécs
6Soproni Erzsébet Teaching Hospital and Rehabilitation Institute, Neurology-stroke,
Introduction: Fabry disease (FD) is the second most common metabolic disorder with high morbidity and mortality. Hundreds of mutations and non-coding haplotypes in the GLA gene have been described; however, many are variants of unknown significance, prompting doubts about the diagnosis and treatment
Aims: Our aim was to identify the rare variants of GLA gene FD patients, as well to classify and evaluate their role in the phenotype of patients.
Methods: We identified GLA mutations in patients with suspicion of FD in Hungary for the last couple of decades. Identification of patients’ genotype was done with Sanger sequencing. Patients tested were participating in FD screening projects or showed typical signs of FD or had low enzyme activity. The detected variants were classified using the current ACMG guideline, Fabry databases and literature.
Results: We found 24 different rare variants in 51 patients overall, of which 16 were classified as pathogenic, 4 likely pathogenic and 4 likely benign. Of the identified variants, 13 cause classic and 7 later onset phenotype. We also identified 2 variants that have conflicting interpretations of pathogenicity. Four of the damaging rare variants were only found in Hungarian patients so far.
Conclusion: We present a descriptive clinical study including 51 patients with 24 different GLA variants. We identified 4 novel rare damaging variants of the GLA gene. In order to better characterise VUS, not only probands but also all asymptomatic variant carriers from Fabry families should be followed prospectively. Data sharing has great importance. These data, in the future, will help to distinguish symptoms attributable to FD from nonspecific comorbidities in benign GLA variants carriers.
Funding: Nothing to disclose.