title: Variable expressivity and genetic heterogeneity involving DPT and SEMA3D genes in autosomal dominant familial Meniere's disease.
abstract: Autosomal dominant (AD) familial Meniere's disease (FMD) is a rare disorder involving the inner ear defined by sensorineural hearing loss, tinnitus and episodic vertigo. Here, we have identified two novel and rare heterozygous variants in the SEMA3D and DPT genes segregating with the complete phenotype that have variable expressivity in two pedigrees with AD-FMD. A detailed characterization of the phenotype within each family illustrates the clinical heterogeneity in the onset and progression of the disease. We also showed the expression of both genes in the human cochlea and performed in silico analyses of these variants. Three-dimensional protein modelling showed changes in the structure of the protein indicating potential physical interactions. These results confirm a genetic heterogeneity in FMD with incomplete penetrance and variable expressivity.
authors.affiliation: Otology & Neurotology Group CTS495, Department of Genomic Medicine, GENYO-Centre for Genomics and Oncological Research-Pfizer/University of Granada/Junta de Andalucía, PTS, Granada, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Martín-Sierra
authors.affiliation: Otology & Neurotology Group CTS495, Department of Genomic Medicine, GENYO-Centre for Genomics and Oncological Research-Pfizer/University of Granada/Junta de Andalucía, PTS, Granada, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Gallego-Martinez
authors.affiliation: Otology & Neurotology Group CTS495, Department of Genomic Medicine, GENYO-Centre for Genomics and Oncological Research-Pfizer/University of Granada/Junta de Andalucía, PTS, Granada, Spain.
authors.forename: Teresa
authors.identifier: 0000-0001-8355-6028
authors.initials: T
authors.lastname: Requena
authors.affiliation: Otology & Neurotology Group CTS495, Department of Genomic Medicine, GENYO-Centre for Genomics and Oncological Research-Pfizer/University of Granada/Junta de Andalucía, PTS, Granada, Spain.
authors.forename: Lidia
authors.initials: L
authors.lastname: Frejo
authors.affiliation: Department of Otolaryngology, Hospital Universitario de Salamanca, Salamanca, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Batuecas-Caletrío
authors.affiliation: Otology & Neurotology Group CTS495, Department of Genomic Medicine, GENYO-Centre for Genomics and Oncological Research-Pfizer/University of Granada/Junta de Andalucía, PTS, Granada, Spain.|Department of Otolaryngology, Instituto de Investigación Biosanitaria ibs. Granada Complejo Hospital Universitario, Granada (CHUGRA), Granada, Spain.
authors.forename: Jose A
authors.identifier: 0000-0002-8583-1430
authors.initials: JA
authors.lastname: Lopez-Escamez
mesh_terms: D000328:Adult; D000368:Aged; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D003051:Cochlea / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005799:Genes, Dominant; D018740:Genetic Heterogeneity; D006801:Humans; D008297:Male; D008575:Meniere Disease / Q000175:diagnosis / Q000235:genetics*; D008875:Middle Aged; D056004:Molecular Dynamics Simulation; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D039961:Semaphorins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; C082019:DPT protein, human; D016326:Extracellular Matrix Proteins; C000592402:Sema3D protein, human; D039961:Semaphorins