title: A novel TECTA mutation causes ARNSHL.
abstract: OBJECTIVE
  Autosomal recessive nonsyndromic hearing loss (ARNSHL) is a genetically heterogeneous sensorineural disorder. Alpha-tectorin, which is encoded by the TECTA gene, is a non-collagenous component of the tectorial membrane in the inner ear defect of which leads to moderate to severe hearing loss (HL).
  
  
  METHODS
  25 unrelated Iranian multiplex ARNSHL families, negative for GJB2 mutations, were recruited in this study. Clinical inspections including audiometric and otologic examinations ruled out syndromic forms. Genetic linkage analysis was performed using six short tandem repeat markers closely linked to DFNB21. Haplotype and LOD score analysis were used to confirm possible linkage. All coding exons of TECTA were subject to DNA sequencing in the linked family.
  
  
  RESULTS
  A novel homozygous variant (c.734G > A) was found in exon 5 of the TECTA gene in one family leading to a nonsense mutation (p.W245×). It co-segregated with HL in the family. This variant was not detected in 50 controls. All affected individuals in the family had moderate to severe HL. It full filled the criteria of a pathogenic variant.
  
  
  CONCLUSIONS
  Our data confirms the phenotype-directed genotyping for DFNB21 deafness against the typical profound HL phenotype seen in the most families segregating ARNSHL. We recommend mutation screening of TECTA in ARNSHL families segregating moderate to severe HL phenotype.
authors.affiliation: Department of Molecular Medicine School of Advanced Technologies in Medicine, Tehran University of Medical Science, Tehran, Iran; Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.
authors.forename: Samira
authors.initials: S
authors.lastname: Asgharzade
authors.affiliation: Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Mohammad Amin
authors.initials: MA
authors.lastname: Tabatabaiefar
authors.affiliation: Department of Molecular Medicine School of Advanced Technologies in Medicine, Tehran University of Medical Science, Tehran, Iran.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Modarressi
authors.affiliation: Department of Molecular Medicine School of Advanced Technologies in Medicine, Tehran University of Medical Science, Tehran, Iran.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Ghahremani
authors.affiliation: Department of Genetics, Faculty of Basic Sciences, University of Shahrekord, Iran.
authors.forename: Somayeh
authors.initials: S
authors.lastname: Reiisi
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Parisa
authors.initials: P
authors.lastname: Tahmasebi
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Abdollahnejad
authors.affiliation: Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address: mchalesh@yahoo.com.
authors.forename: Morteza Hashemzadeh
authors.initials: MH
authors.lastname: Chaleshtori
mesh_terms: D001299:Audiometry; D001301:Audiometry, Pure-Tone; D005091:Exons; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D008040:Genetic Linkage; D005838:Genotype; D006239:Haplotypes; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007492:Iran; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D017422:Sequence Analysis, DNA
chemical_list: D016326:Extracellular Matrix Proteins; D058851:GPI-Linked Proteins; C491350:TECTA protein, human
keywords: Hearing loss; Iran; Linkage analysis; Mutation; TECTA