Akademik Veri Yönetim Sistemi
58th European Society of Human Genetics (ESHG) Conference, Milan, İtalya, 24 - 27 Mayıs 2025, cilt.33, sa.1, ss.190-191, (Özet Bildiri)
Background: Essential tremor (ET) is one of the most common neurological disorders, primarily characterized by a postural or kinetic tremor that starts asymmetrically and progressively involves bilaterally towards contralateral sides. While usually seen as arm tremors, some patients also experience tremors in areas like the head. Genetic and molecular mechanisms in ET are poorly understood due to genetic heterogeneity, variable expression, and overlapping phenotypes, and our goal is to identify the molecular etiology in affected families.
Material and methods: Exome sequencing was conducted for five patients from three families, including three from one family as a trio. Sanger sequencing is used for confirmation and segregation. Additionally, repeat variations in NOTCH2NLC and GIPC1 were screened by using an in-house designed TP-PCR assay.
Results: Heterozygous/novel missense variants in GABRR2 and FTL were found in Family-I with titubation and liver disease, in GABBR1 in Family-II with titubation and hand tremor, and in GABRP in Family-III with bilateral rest and postural tremor. GABA-receptor subunit knockout mice exhibit tremors and motor incoordination resembling human ET.
Conclusion: This study highlights the GABAergic dysfunction in the major motor pathway and potential targets for pharmacotherapy of ET. Identifying molecular mechanisms is key to improving ET management and treatment.