Frequency of Usher syndrome in two pediatric populations: Implications for genetic screening of deaf and hard of hearing children.
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.
Kimberling
William J
WJ
Department of Genetics, Boys Town National Research Hospital, Omaha, Nebraska 68131, USA. bkimberling@gmail.com
Hildebrand
Michael S
MS
Shearer
A Eliot
AE
Jensen
Maren L
ML
Halder
Jennifer A
JA
Trzupek
Karmen
K
Cohn
Edward S
ES
Weleber
Richard G
RG
Stone
Edwin M
EM
Smith
Richard J H
RJ
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
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