A recent study has unveiled significant findings about the genetic epidemiology of amyotrophic lateral sclerosis (ALS) within the Greek-Cypriot population, providing valuable insights as researchers work toward personalized medicine approaches for this devastating condition.
Amyotrophic lateral sclerosis is characterized by the progressive degeneration of motor neurons, leading to muscle weakness and atrophy. This research, conducted by the Cyprus Institute of Neurology and Genetics, marks the first comprehensive genetic epidemiology study focused on ALS among Greek-Cypriots.
The research examined 89 patients diagnosed with ALS—divided between familial (fALS) and sporadic cases (sALS). Results indicated C9orf72 hexanucleotide repeat expansions as the predominant genetic cause of ALS among participants, accounting for 22.47% of cases.
The study revealed other notable findings, including the identification of variants across six additional ALS-associated genes, which highlights the genetic diversity of the condition. With familial cases comprising 23.6% of the study population, this ratio exceeded the rates observed elsewhere, hinting at potential unique genetic factors prevalent within the Greek-Cypriot demographic.
The crude prevalence of ALS was estimated at 6.6 cases per 100,000 people within the government-controlled areas of Cyprus, showcasing differences when compared to broader European statistics. The incidence for the period spanning 2022 to 2023 was reported to be 1.38 cases per 100,000, slightly below the European median.
Importantly, the study identified a higher frequency of female patients within familial ALS cases compared to sporadic ones, emphasizing potential gender-related genetic risks. Traditionally, ALS has been considered to affect more males than females, but this study’s results suggest shifting trends, possibly influenced by changing lifestyles and environmental exposures.
The researchers noted, "The C9orf72 repeat expansion is the most predominant ALS genetic cause in Cyprus, with a frequency of 22.47%." Further emphasizing the importance of these findings, they added, "Our findings revealed important regional variations and found pathogenic ALS variants in both familial and sporadic ALS cases, with C9orf72 being the most common causative ALS gene." These insights pave the way for targeted genetic screenings, which could play pivotal roles in diagnosing and treating patients effectively.
By utilizing next-generation sequencing, the researchers were able to identify rare variants and assess their potential pathogenicity. Analyzed genes included TARDBP, TBK1, FIG4, GLT8D1, and BICD2—each linked to ALS pathology. Additional variants were present, albeit at frequencies lower than those reported elsewhere.
This investigation not only sheds light on the genetic mutations associated with ALS among Greek-Cypriots but also helps establish baseline data for future studies. With the various genetic factors contributing to ALS still not fully understood, this research enhances current knowledge and emphasizes the necessity for continued exploration.
Further research is encouraged, particularly among genetically undiagnosed patients, to comprehensively delineate involvement of other potential ALS-related genes unique to this population. The findings indicate novel gene variations may reside within this specific demographic, underscoring the need for enhanced genetic screening and studies to investigate these potential links.
The study has been ethically approved and has received funding from Telethon, Cyprus. Overall, this landmark research lays the foundation for more personalized approaches to treating ALS, directly addressing the unique genetic backdrop of the Greek-Cypriot population.