Founder Effect of Q422X Mutation as a Cause of Fucosidosis in Cuba

Abstract

Introduction: Fucosidosis is a neurodegenerative disease with a very broad spectrum of clinical findings, caused by the loss of activity of the lysosomal enzyme α-L-fucosidase. Approximately 130 patients have been diagnosed worldwide. In Cuba, all affected families come from Holguín province. Objective: To molecularly characterize fucosidosis in Cuba. Methods: The presence of Q422X mutation was studied in all patients, as well as in relatives with a priori risk of being carriers, by polymerase chain reaction, using the primers FUCA1 F30 and FUCA2 F2r. The families were grouped according to the place of origin of the ancestors and the existence of consanguinity within them was identified. Results: The 19 patients diagnosed enzymatically presented Q422X mutation in double dose. All parents studied and 50% of clinically healthy siblings and half-siblings were heterozygous. The families of 94.7% of those affected were located in the northeast of Holguín municipality and rural localities of three neighboring municipalities. The frequency of parental consanguinity was 52.6%. Conclusions: Fucosidosis in Holguín province has high frequency as a consequence of the founder effect of Q422X mutation, which was introduced by genetic drift as the only causal mutation and was maintained over time due to the difficult access to remote localities, parental consanguinity and genetic isolation due to socioeconomic reasons.