Limbic System Associated Membrane Protein Mutation in an Iranian Family Diagnosed with Ménière's Disease.

Archives of Iranian medicine 2020 May 01

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Ménière's disease (MD) is a common inner ear disorder which is characterized by recurrent attacks of vertigo, fluctuating sensorineural hearing loss (SNHL), tinnitus, and a sense of fullness in the affected ear. MD is a complex disorder; although six genes have been linked to familial autosomal dominant form of the disease, in many cases, the exact genetic etiology remains elusive. To elucidate the genetic causes of MD in an Iranian family, we performed exome sequencing on all members of the family: consanguineous parents and four children (two affected and two unaffected). Variant filtering was completed using a customized workflow keeping variants based on segregation with MD in autosomal recessive (AR) inheritance pattern, minor allele frequency (MAF), and in-silico prediction of pathogenicity. Analysis revealed that in this family, 970 variants co-segregated with MD in AR pattern, out of which eight variants (one intergenic, four intronic, and three exonic) were extremely rare. The exonic variants included a synonymous substitution in USP3 gene, an in-frame deletion in ZBED2 gene, and a rare, highly conserved deleterious missense alteration in LSAMP gene. The phenotype observed in the proband described here, i.e. vertigo, poor sense of smell, tinnitus, and borderline hearing ability, may originate from aberrant changes in the cerebellum and limbic system due to a deleterious mutation in the LSAMP gene; hence, LSAMP mutation is a possible candidate for the etiology of MD in this family. © 2020 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Citation

Zohreh Mehrjoo, Kimia Kahrizi, Marzieh Mohseni, Mojdeh Akbari, Sanaz Arzhangi, Khadijeh Jalalvand, Hossein Najmabadi, Mohammad Farhadi, Mohammad Mohseni, Alimohamad Asghari, Saleh Mohebbi, Ahmad Daneshi. Limbic System Associated Membrane Protein Mutation in an Iranian Family Diagnosed with Ménière's Disease. Archives of Iranian medicine. 2020 May 01;23(5):319-325