High Prevalence Mutations in ALMS1 in Spanish Alström Patients

Abstract Background:Alström syndrome (ALMS) is a rare disease with an estimated prevalence lower than 1 in 1,000,000. It is associated with mutations in the Alström syndrome 1 (ALMS1) gene, which codifies for a structural protein of the basal body and centrosomes. Symptomatology involves nystagmus, type 2 diabetes mellitus (DM2), obesity, dilated cardiomyopathy (DMC), neurodegenerative disorders and multi-organ fibrosis.Methods:We included the clinical data of 13 patients from 12 families, all of them from Spain. We studied the allelic frequency for the different mutations present in this cohort and we perform a haplotype analysis for the most prevalent allele.Results:Two alleles were detected in high frequency: p.(Tyr1714Ter) (0,25) and p.(Ser3872TyrfsTer19) (0,167). The segregation analysis of the mutation p.(Tyr1714Ter) in 3 families shows that it is linked to a rare missense polymorphism. Also, we detect an ancestral haplotype for ALMS1 in three families.Conclusion:Mutation p.(Tyr1714Ter) co-segregates with a rare single nucleotide polymorphism (SNP) that could be arise by a founder effect in the Iberian Peninsula.