title: Molecular study of patients with auditory neuropathy.
abstract: Auditory neuropathy is a type of hearing loss that constitutes a change in the conduct of the auditory stimulus by the involvement of inner hair cells or auditory nerve synapses. It is characterized by the absence or alteration of waves in the examination of brainstem auditory evoked potentials, with otoacoustic and/or cochlear microphonic issues. At present, four loci associated with non‑syndromic auditory neuropathy have been mapped: Autosomal recessive deafness‑9 [DFNB9; the otoferlin (OTOF) gene] and autosomal recessive deafness‑59 [DFNB59; the pejvakin (PJVK) gene], associated with autosomal recessive inheritance; the autosomal dominant auditory neuropathy gene [AUNA1; the diaphanous‑3 (DIAPH3) gene]; and AUNX1, linked to chromosome X. Furthermore, mutations of connexin 26 [the gap junction β2 (GJB2) gene] have also been associated with the disease. OTOF gene mutations exert a significant role in auditory neuropathy. In excess of 80 pathogenic mutations have been identified in individuals with non‑syndromic deafness in populations of different origins, with an emphasis on the p.Q829X mutation, which was found in ~3% of cases of deafness in the Spanish population. The identification of genetic alterations responsible for auditory neuropathy is one of the challenges contributing to understand the molecular bases of the different phenotypes of hearing loss. Thus, the present study aimed to investigate molecular changes in the OTOF gene in patients with auditory neuropathy, and to develop a DNA chip for the molecular diagnosis of auditory neuropathy using mass spectrometry for genotyping. Genetic alterations were investigated in 47 patients with hearing loss and clinical diagnosis of auditory neuropathy, and the c.35delG mutation in the GJB2 gene was identified in three homozygous patients, and the heterozygous parents of one of these cases. Additionally, OTOF gene mutations were tracked by complete sequencing of 48 exons, although these results are still preliminary. Studying the genetic basis of auditory neuropathy is of utmost importance for obtaining a differential diagnosis, developing more specific treatments and more accurate genetic counseling.
authors.affiliation: Otology, Audiology and Implantable Ear Prostheses, Ear, Nose, Throat and Head and Neck Surgery Department, State University of Campinas (UNICAMP), São Paulo 13081‑970, Brazil.
authors.forename: Guilherme Machado De
authors.initials: GM
authors.lastname: Carvalho
authors.affiliation: Human Molecular Genetics Laboratory, Molecular Biology and Genetic Engineering Center‑CBMEG, State University of Campinas (UNICAMP), São Paulo 13081‑970, Brazil.
authors.forename: Priscila Zonzini
authors.initials: PZ
authors.lastname: Ramos
authors.affiliation: Otology, Audiology and Implantable Ear Prostheses, Ear, Nose, Throat and Head and Neck Surgery Department, State University of Campinas (UNICAMP), São Paulo 13081‑970, Brazil.
authors.forename: Arthur Menino
authors.initials: AM
authors.lastname: Castilho
authors.affiliation: Otology, Audiology and Implantable Ear Prostheses, Ear, Nose, Throat and Head and Neck Surgery Department, State University of Campinas (UNICAMP), São Paulo 13081‑970, Brazil.
authors.forename: Alexandre Caixeta
authors.initials: AC
authors.lastname: Guimarães
authors.affiliation: Human Molecular Genetics Laboratory, Molecular Biology and Genetic Engineering Center‑CBMEG, State University of Campinas (UNICAMP), São Paulo 13081‑970, Brazil.
authors.forename: Edi Lúcia
authors.initials: EL
authors.lastname: Sartorato
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D005091:Exons; D005260:Female; D050259:Genes, Mitochondrial; D056726:Genetic Association Studies; D005838:Genotype; D006313:Hearing Loss, Central / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; C118457:OTOF protein, human