Abstract
Usher syndrome is a frequent cause of the combination of deafness and blindness due to retinitis pigmentosa (RP). Five genes are known to underlie different forms of Usher syndrome type I (USH1). In the Ashkenazi Jewish population, the R245X mutation of the PCDH15 gene may be the most common cause of USH1 (Ben-Yosef T, Ness SL, Madeo AC, Bar-Lev A, Wolfman JH, Ahmed ZM, Desnick RK, Willner JP, Avraham KB, Ostrer H, Oddoux C, Griffith AJ, Friedman TB N Engl J Med 348: 1664–1670, 2003). To estimate what percentage of Ashkenazi Jewish children born with profound hearing loss will develop RP due to R245X, we examined the prevalence of the R245X PCDH15 mutation and its carrier rate among Ashkenazi Jews in Israel. Among probands diagnosed with nonsyndromic hearing loss not due to mutations of connexin 26 (GJB2) and/or connexin 30 (GJB6), and below the age of 10, 2 of 20 (10%) were homozygous for the R245X mutation. Among older nonsyndromic deaf individuals, no homozygotes were detected, although one individual was heterozygous for R245X. The carrier rate of the R245X mutation among the normal hearing Ashkenazi population in Israel was estimated at 1%. Ashkenazi Jewish children with profound prelingual hearing loss should be evaluated for the R245X PCDH15 mutation and undergo ophthalmologic evaluation to determine whether they will develop RP. Rehabilitation can then begin before loss of vision. Early use of cochlear implants in such cases may rescue these individuals from a dual neurosensory deficit.
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Abbreviations
- ERG:
-
electroretinograms
- SNHL:
-
sensorineural hearing loss
- RP:
-
retinitis pigmentosa
- USH1:
-
Usher syndrome type 1
- USH2:
-
Usher syndrome type 2
- USH3:
-
Usher syndrome type 3
- NSHL:
-
nonsyndromic hearing loss
- PCDH15:
-
protocadherin 15
- ASPCR:
-
allele-specific PCR
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Acknowledgements
The authors thank the family members for their generous cooperation in this study and Mira Berlin, Bella Davidov, Miri Yanuv, Batsheva Bonne-Tamir, and Andrew Griffith for their contributions.
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Supported by the Israel Ministry of Science, Culture and Sport (K.B.A.), the European Community (QLG2-1999-00988) (K.B.A.), and the National Institute on Deafness and Other Communication Disorders intramural research project ZO1 DC000039-06 (T.B.F.).
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Brownstein, Z., Ben-Yosef, T., Dagan, O. et al. The R245X Mutation of PCDH15 in Ashkenazi Jewish Children Diagnosed with Nonsyndromic Hearing Loss Foreshadows Retinitis Pigmentosa. Pediatr Res 55, 995–1000 (2004). https://doi.org/10.1203/01.PDR.0000125258.58267.56
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DOI: https://doi.org/10.1203/01.PDR.0000125258.58267.56
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