title: Variable degrees of hearing impairment in a Dutch DFNX4 (DFN6) family.
abstract: OBJECTIVE
  Investigation of the audiometric characteristics of a large Dutch DFNX4 family with a p.Glu72X mutation in the SMPX gene.
  
  
  METHODS
  Sixty family members participated in this study and examination consisted of medical history, otoscopy, pure tone and speech audiometry. Linkage and mutation analysis revealed a pathogenic mutation in the SMPX gene.
  
  
  RESULTS
  All 25 mutation carriers exhibited hearing impairment, except one woman aged 25 years. The men (n = 10) showed more severe hearing impairment than the women (n = 14) and already at a younger age. The age of onset according to history was 2-10 years (mean: 3.3 years) in men and 3-48 years (mean: 26.4 years) in women. In the men, severe threshold deterioration mainly occurred during the first two decades of life, especially at the higher frequencies. The women showed milder threshold deterioration and more pronounced across-subjects and individual inter-aural variation, especially at 2-8 kHz. Longitudinal linear regression analysis demonstrated significant progression of at least two frequencies in five individuals (3 men and 2 women). The speech recognition scores of the mutation carriers with hearing impairment were decreased at relatively young ages compared to a reference group of patients with only presbycusis, especially in men. However, all these patients tended to have better speech recognition scores than the presbycusis patients at matching PTA(1,2,4 kHz) levels.
  
  
  CONCLUSIONS
  This study demonstrates the phenotypic heterogeneity in this large family with an X-linked pattern of inherited sensorineural hearing impairment. The men showed more severe hearing impairment at a younger age with more pronounced progression during the first two decades of life, while women demonstrated less severe hearing impairment with more gradual progression and a wider variation in age of onset, degree of hearing impairment and inter-aural asymmetry in thresholds.
authors: Department of Otorhinolaryngology, Head and Neck Surgery, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. N.Weegerink@kno.umcn.nl
authors: N J D
authors: NJ
authors: Weegerink
authors: P L M
authors: PL
authors: Huygen
authors: M
authors: M
authors: Schraders
authors: H
authors: H
authors: Kremer
authors: R J E
authors: RJ
authors: Pennings
authors: H P M
authors: HP
authors: Kunst
mesh_terms: D000161:Acoustic Stimulation; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001301:Audiometry, Pure-Tone; D001302:Audiometry, Speech; D001307:Auditory Perception / Q000235:genetics*; D001309:Auditory Threshold; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D040941:Heredity; D006801:Humans; D016014:Linear Models; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D009154:Mutation; D009426:Netherlands; D017711:Nonlinear Dynamics; D038781:Otoscopy; D019986:Persons with Hearing Disabilities / Q000523:psychology; D010641:Phenotype; D012027:Reflex, Vestibulo-Ocular / Q000235:genetics; D012720:Severity of Illness Index; D012737:Sex Factors; D013067:Speech Perception / Q000235:genetics; D055815:Young Adult
chemical_list: D009124:Muscle Proteins; C433890:SMPX protein, human