Epidemiological and population genetic characterization of fucosidosis in Holguin province, Cuba

Introduction: Fucosidosis is a rare lysosomal storage disease, of which in Cuba, patients have been reported only in Holguín province.Objective: to characterize the epidemiological and genetic-population behavior of fucosidosis in Holguín province.Method: A case series study was carried out, whose universe and sample included all families with patients with fucosidosis, diagnosed between 1985 and 2023. Birth prevalence, mortality rate, attributable mortality, and consanguinity rate were calculated. Gene and genotypic frequencies were estimated from the prevalence. A Hardy-Weinberg test for the analysis of gene equilibrium at the FUCA 1 locus was applied to the results of the genotypic characterization for the Q427X mutation.Results: 19 patients were diagnosed, belonging to 13 families, which represented a birth prevalence of 3.28 x 105 live births. The case fatality and parental consanguinity rates were 0.84 and 0.53 respectively. The estimated frequencies of the recessive allele and the heterozygous genotype were 0.0057271 and 0.0113887, respectively, so approximately 11,660 people in the population of the Holguín province at the end of 2023 must have been carriers. The existence of gene equilibrium for the FUCA1 locus in the population genotypically characterized for the Q427X mutation suggests that the affected families have remained in the original region, and systematic and stochastic factors that alter gene frequencies, including the existence of gene flow, have not occurred since the apparition of the disease due to a founder effect. The mutation rate of the gene must have remained constant according to the selection coefficient at the locus, corresponding to a lethal disease whose fitness is zero.Conclusions: The prevalence of fucosidosis in Holguín province is one of the highest worldwide and is the result of the combination of the founder effect due to genetic drift of the Q427X mutation, with parental consanguinity and genetic isolation due to socioeconomic causes