A Meniere's disease gene linked to chromosome 12p12.3
Joakim Klar1, Carina Frykholm, Ulla Friberg
1Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Abstract:
Meniere's disease (MD) is characterized by spontaneous attacks of vertigo, fluctuating sensorineural hearing loss, tinnitus, and aural fullness. The majority of patients with MD appear sporadic but 5%-13% of the cases have a family history for the disease. The cause of both the sporadic and inherited forms of MD remains unclear despite a number of candidate genes defined from their association with hearing loss. We have performed a genome wide linkage scan on a large Swedish family segregating MD in five generations. Five candidate regions with a lod score of >1 were identified. Two additional families with autosomal dominant MD were analyzed for linkage to these regions and a cumulative Z(max) of 3.46 was obtained for a single region on chromosome 12p. In two of the three families, a shared haplotype was found to extend over 1.7 Mb which suggests a common ancestral origin. Within this region, a single recombination event restricts the candidate region to 463 kb.
Insights
Researchers identified a specific gene region on chromosome 12p linked to Meniere
Area of Science:
- Genetics
- Otolaryngology
- Neurology
Background:
- Meniere's disease (MD) presents with vertigo, hearing loss, tinnitus, and aural fullness.
- While often sporadic, 5-13% of MD cases have a family history, suggesting genetic factors.
- The genetic underpinnings of MD remain largely unknown.
Purpose of the Study:
- To identify genetic loci associated with Meniere's disease in a large Swedish family.
- To investigate potential shared genetic origins in families with autosomal dominant MD.
Main Methods:
- Genome-wide linkage scan performed on a five-generation Swedish family with MD.
- Analysis of two additional families with autosomal dominant MD.
- Linkage analysis to identify candidate regions and refine the disease locus.
Main Results:
- Five candidate regions with a lod score >1 were identified.
- A single region on chromosome 12p showed significant linkage (cumulative Z(max) = 3.46) across three families.
- A shared haplotype in two families narrowed the candidate region to 463 kb, suggesting a common ancestor.
Conclusions:
- A specific locus on chromosome 12p is implicated in autosomal dominant Meniere's disease.
- This finding provides a critical step towards understanding the genetic basis of MD.
- Further investigation within this refined region may reveal the causative gene(s).
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