title: Frequency of Usher syndrome in two pediatric populations: Implications for genetic screening of deaf and hard of hearing children.
abstract: OBJECTIVE
  Usher syndrome is a major cause of genetic deafness and blindness. The hearing loss is usually congenital and the retinitis pigmentosa is progressive and first noticed in early childhood to the middle teenage years. Its frequency may be underestimated. Newly developed molecular technologies can detect the underlying gene mutation of this disorder early in life providing estimation of its prevalence in at risk pediatric populations and laying a foundation for its incorporation as an adjunct to newborn hearing screening programs.
  
  
  METHODS
  A total of 133 children from two deaf and hard of hearing pediatric populations were genotyped first for GJB2/6 and, if negative, then for Usher syndrome. Children were scored as positive if the test revealed > or =1 pathogenic mutations in any Usher gene.
  
  
  RESULTS
  Fifteen children carried pathogenic mutations in one of the Usher genes; the number of deaf and hard of hearing children carrying Usher syndrome mutations was 15/133 (11.3%). The population prevalence was estimated to be 1/6000.
  
  
  CONCLUSIONS
  Usher syndrome is more prevalent than has been reported before the genome project era. Early diagnosis of Usher syndrome has important positive implications for childhood safety, educational planning, genetic counseling, and treatment. The results demonstrate that DNA testing for Usher syndrome is feasible and may be a useful addition to newborn hearing screening programs.
authors.affiliation: Department of Genetics, Boys Town National Research Hospital, Omaha, Nebraska 68131, USA. bkimberling@gmail.com
authors.forename: William J
authors.initials: WJ
authors.lastname: Kimberling
authors.forename: Michael S
authors.initials: MS
authors.lastname: Hildebrand
authors.forename: A Eliot
authors.initials: AE
authors.lastname: Shearer
authors.forename: Maren L
authors.initials: ML
authors.lastname: Jensen
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Halder
authors.forename: Karmen
authors.initials: K
authors.lastname: Trzupek
authors.forename: Edward S
authors.initials: ES
authors.lastname: Cohn
authors.forename: Richard G
authors.initials: RG
authors.lastname: Weleber
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
authors.forename: Richard J H
authors.initials: RJ
authors.lastname: Smith
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000293:Adolescent; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics; D018797:Cell Cycle Proteins; D000072259:Connexin 26; D000075302:Connexin 30; D017630:Connexins / Q000235:genetics*; D003598:Cytoskeletal Proteins; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D009154:Mutation / Q000235:genetics; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics; D009922:Oregon / Q000453:epidemiology; D015995:Prevalence; D017422:Sequence Analysis, DNA; D011795:Surveys and Questionnaires; D052245:Usher Syndromes / Q000453:epidemiology* / Q000235:genetics*; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C442480:CDH23 protein, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; D018797:Cell Cycle Proteins; D000075302:Connexin 30; D017630:Connexins; D003598:Cytoskeletal Proteins; D016326:Extracellular Matrix Proteins; C000607042:GJB2 protein, human; C491020:GJB6 protein, human; C000631455:MYO7A protein, human; D000081412:Myosin VIIa; C118970:USH1C protein, human; C112735:USH2A protein, human; D000072259:Connexin 26; D009218:Myosins