Genetic profile of Charcot-Marie-Tooth disease in the Saudi population: A retrospective study highlighting the role of consanguinity.

To identify the genetic landscape of CMT in Saudi Arabia. This retrospective cohort study included 43 patients diagnosed with CMT between 2016 and 2022 at National Guard Health Affairs hospitals in three cities. All CMT cases with a genetic diagnosis were included. Genetic testing was conducted in 23 out of 43 CMT cases (53%), and clinically relevant genetic variants associated with CMT were identified in 17 of 23 patients (73.9%). The most common genes in the cohort were MTMR2, PMP22, and FGD4, with notable intra-tribe mutations suggesting a strong influence of consanguinity. The predominant mode of inheritance was autosomal recessive CMT1, affecting 12 out of 17 cases (70.6%). Five novel variants associated with CMT were identified in MTMR2, PRX, SBF1, and HSPB8. This study reveals a distinct genetic profile of CMT in the Saudi population, with a higher prevalence of autosomal recessive forms of the disease compared to other populations. The findings highlight the importance of incorporating genetic testing into routine clinical practice, particularly in populations with high consanguinity rates.