Genetic and Clinical Insights into ALS/FTD: Profiling a Rare Cohort to Explore Spectrum Heterogeneity

Area of Science:

• Neuroscience
• Genetics

Background:

• Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders with overlapping features.
• The C9orf72 repeat expansion is a common genetic cause, driving research into disease heterogeneity.
• Genetic modifiers may influence ALS/FTD variability.

Purpose of the Study:

• To analyze C9orf72 repeat expansion frequency in Serbian ALS/FTD patients.
• To investigate the potential modifying roles of APOE, ATXN1, and ATXN2 in ALS/FTD.
• To explore genetic factors contributing to ALS/FTD heterogeneity.

Main Methods:

• Included 22 ALS/FTD patients and 94 healthy controls.
• Used fluorescent PCR and capillary electrophoresis for C9orf72, ATXN1, and ATXN2 repeat sizing.
• Employed repeat-primed PCR for C9orf72 expansion confirmation and real-time PCR for APOE genotyping.

Main Results:

• 31.82% of ALS/FTD patients had heterozygous C9orf72 repeat expansion.
• APOE ε3/ε3 was the most common genotype (72.73%) in patients.
• No significant differences in APOE ε4 frequency or intermediate ATXN1/ATXN2 repeats were found between patients and controls.

Conclusions:

• Larger, population-specific studies are required to elucidate the role of genetic modifiers in ALS/FTD.
• Understanding genetic modifiers is crucial for developing precision medicine strategies for ALS/FTD.
• This study contributes to understanding genetic influences on ALS/FTD pathogenesis.