The R245X mutation of PCDH15 in Ashkenazi Jewish children diagnosed with nonsyndromic hearing loss foreshadows retinitis pigmentosa
The R245X mutation of PCDH15 in Ashkenazi Jewish children diagnosed with nonsyndromic hearing loss foreshadows retinitis pigmentosa
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DOI：
10.1203/01.pdr.0000125258.58267.56
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发表时间：
2004-06-01
影响因子：
3.6
通讯作者：
Avraham, KB
中科院分区：
文献类型：
--
作者：
Brownstein, Z;Ben-Yosef, T;Avraham, KB
Usher综合征是视网膜色素变性（RP）导致耳聋和失明的常见原因。已知有五种基因是不同形式的Usher综合征I型（USH 1）的基础。在德系犹太人群体中，PCDH 15基因的R245 X突变可能是USH 1的最常见原因（Ben-Yosef T. Ness SL，Madeo AC，Bar-Lev A，Wolfman JH，Ahmed ZM，Desnick RK，Willner JP，Avraham KB.奥斯特雷湾奥杜角Griffith AJ，Friedman TB N Enol J Med 348：1664-1670 2003）。为了估计出生时患有严重听力损失的德系犹太儿童中有多少百分比会因R245 X而发展为RP，我们检查了以色列德系犹太人中R245 X PCDH 15突变的患病率及其携带率。在被诊断为非连接蛋白26（GJB 2）和/或连接蛋白30（GJB 6）突变所致的非综合征性听力损失的先证者中，年龄小于10岁的患者中，20例中有2例（10%）为R245 X突变纯合子。在老年非综合征性耳聋患者中。没有检测到纯合子，尽管有一个个体是R245 X杂合子。在以色列听力正常的德系犹太人中，R245 X突变的携带率估计为1%。患有严重语前听力损失的德系犹太儿童应进行R245 X PCDH 15突变的评估，并进行眼科评估，以确定他们是否会发展为RP。康复可以在视力丧失之前开始。在这种情况下，早期使用人工耳蜗植入可能会将这些人从双重神经感觉缺陷中拯救出来。
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 Enol 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.