Mutation screening of the Otop1 gene in familial benign positional paroxysmal vertigo

Objectives: Benign paroxysmal positional vertigo (BPPV) is a sporadic disorder in the vast majority of cases, although a familial, benign, recurrent form, in which the disease segregates in an autosomal dominant fashion has been described. After the evidence for a role of a novel murine gene, Otop1, in knock-out tlt (tilted) and mlh (Mergulhador) mice, lacking the perception of gravity and linear motion and showing a vestibular disorder due to non-syndromic agenesis of both utricular and saccular otoconia, we aimed at verifying the role of the human analogue of the Otop1 gene in BPPV pathogenesis in familial cases of BPPV, collected in our tertiary university referral centre. Methods: Starting in 2007, families with at least two living members thought to have BPPV were considered for inclusion in the present study. The cases were both retrospectively and prospectively identified over the following two years. Results: Seven familial aggregations of BPPV were identified and Otop1 mutation screening showed the presence of a heterozygous mutation in one family, c.1013G> C p.Arg338Pro, which was considered possibly deleterious using the prediction software. It was absent in 100 control alleles, but was also found in two as yet unaffected relatives. Conclusions: The results of a mutation screening of the Otop1 gene in familial cases of BPPV do not support a major role of the gene in the pathogenesis of the disease.