title: Novel mutation in the homeobox domain of transcription factor POU3F4 associated with profound sensorineural hearing loss.
abstract: BACKGROUND
  Hearing loss affects 1 to 3 in 1,000 newborns, with 50% of these cases because of genetic causes. The majority of these are nonsyndromic (70%), and 2% are X linked. So far, 6 different X-linked loci have been mapped, but the causative gene POU3F4 has been identified only for the Locus DFN3. Clinical features of DFN3 often include a mixed, progressive hearing loss, temporal bone anomalies, and stapes fixation. POU3F4 belongs to a subfamily of transcription factors, which are characterized by 2 conserved deoxyribonucleic acid-binding domains, a POU and a HOX domain, both helix-turn-helix structural deoxyribonucleic acid-binding motifs.Several reports have described mutations of POU3F4 in patients with hearing loss and temporal bone abnormalities. In this study, we describe the clinical features and genetic analysis of a male child from a German family with congenital deafness and a novel POU3F4 mutation.
  
  
  METHODS
  Mutational analysis of the affected individual and first-degree relatives was performed using direct sequencing of the coding exon and intron transitions of POU3F4.
  
  
  RESULTS
  The patient (II-1) had profound hearing loss, a severely dysplastic cochlea, and cerebrospinal fluid gusher during cochlear implantation. Sequence analysis of all family members demonstrated a novel missense mutation at nucleotide position 973, thymine to adenine (c.973 T>A), p.W325R in the patient (II-1), the mother (I-2), and sisters (II-2, II-3) heterozygous. The father (I-1) is not a carrier of the mutation. Conservation of the affected amino acid residue was seen across a number of different species.
  
  
  CONCLUSIONS
  We identified a novel mutation in the third helix of the HOX domain of the POU3F4 transcription factor associated with congenital hearing loss.
authors.affiliation: Department of Oto-Rhino-Laryngology, Head and Neck Surgery, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schild
authors.forename: Erick
authors.initials: E
authors.lastname: Prera
authors.forename: Nicola
authors.initials: N
authors.lastname: Lüblinghoff
authors.forename: Susan
authors.initials: S
authors.lastname: Arndt
authors.forename: Antje
authors.initials: A
authors.lastname: Aschendorff
authors.forename: Ralf
authors.initials: R
authors.lastname: Birkenhäger
mesh_terms: D002648:Child; D004252:DNA Mutational Analysis; D006312:Hearing Loss, Bilateral / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D050809:POU Domain Factors / Q000235:genetics*
chemical_list: D050809:POU Domain Factors; C091774:POU3F4 protein, human