Locus for Familial Migrainous Vertigo Disease Maps to Chromosome 5q35

Abstract

Objectives: Migrainous vertigo (episodic vertigo associated with migraine) is sometimes inherited as an autosomal dominant trait. However, neither disease genes nor loci that might be responsible have been reported. We sought to map the genetic locus for familial migrainous vertigo in a 4-generation family and to define the progression of disease in this family. Methods: We studied 23 members in a family in whom migrainous vertigo was inherited as an autosomal dominant trait. Clinical information obtained included case histories and results of otolaryngological, neurologic, audiometric, and imaging evaluations. Genome-wide linkage analysis was performed with Affymetrix Genechip Human Mapping 10K microarrays. Genotyping of family members' DNA with microsatellite markers was used to further assess candidate loci identified from the whole-genome scan. Results: Of 23 family members, 10 suffered from migrainous vertigo beginning after 35 years of age. Migraine headaches usually preceded the onset of vertigo by 15 to 20 years. Longitudinal audiometric studies over 12 years showed stable, high-frequency sensorineural hearing loss consistent with presbycusis. Low-frequency or fluctuating hearing loss was not observed. The results of vestibular testing and imaging studies were unremarkable. Genetic analysis defined a 12.0 MB interval on chromosome 5q35 between loci rs244895 and D5S2073 that contained the disease gene (logarithm of odds score, 4.21). Conclusions: We report the first locus for familial migrainous vertigo, which mapped to 5q35.