Genome-wide SNP genotyping identifies the Stereocilin (STRC) gene as a major contributor to pediatric bilateral sensorineural hearing impairment.
Genome-wide SNP genotyping identifies the Stereocilin (STRC) gene as a major contributor to pediatric bilateral sensorineural hearing impairment.
复制标题
全基因组SNP基因分型鉴定立体纤维蛋白（Strc）基因是小儿双边感觉神经性听力障碍的主要因素。
DOI：
10.1002/ajmg.a.34391
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发表时间：
2012-02
影响因子：
2
通讯作者：
Krantz, Ian D.
中科院分区：
文献类型：
--
作者：
Francey, Lauren J.;Conlin, Laura K.;Kadesch, Hanna E.;Clark, Dinah;Berrodin, Donna;Sun, Yi;Glessner, Joe;Hakonarson, Hakon;Jalas, Chaim;Landau, Chaim;Spinner, Nancy B.;Kenna, Margaret;Sagi, Michal;Rehm, Heidi L.;Krantz, Ian D.
关键词：
听力损失是人类最普遍的感觉知觉缺陷，影响1/500的新生儿，可以是综合征或非综合征，并且是遗传异质性的。近80%的遗传性非综合征型双侧感音神经性听力损失（NBSNHI）是常染色体隐性遗传。虽然许多致病基因已被确定，大多数是次要的贡献者，除了GJB 2，它占近50%的所有隐性病例的严重到极深的先天性NBSNHI在一些人群中。超过60%的NBSNHI儿童没有可识别的遗传原因。为了确定遗传贡献者，我们用NBSNHI对659名GJB 2突变阴性的儿科先证者进行基因分型，并测定拷贝数变异（CNV）。在该队列中鉴定出8名轻中度NBSNHI先证者，其Chr15q15.3缺失包含Stereocilin（STRC）基因，在这些先证者以及50名先证者和14名轻中度NBSNHI同胞和40名GJB 2突变阴性的中度重度-深度NBSNHI先证者中进行STRC测序。与STRC编码区具有99.6%同源性的STRC假基因的存在使得测序解释变得复杂。我们在轻度-中度队列中确定了7/50的先证者在STRC中具有双等位基因改变，不包括先前确定的8个缺失。我们还确定了2/40的先证者在中度严重-深度NBSNHI队列中具有双等位基因改变，值得注意的是，在该队列中没有发现与另一种变体组合的大缺失。这些数据表明，STRC可能是GJB 2突变阴性先证者中NBSNHI的常见贡献者，特别是在轻度至中度听力障碍的患者中。
Hearing loss is the most prevalent sensory perception deficit in humans, affecting 1/500 newborns, can be syndromic or nonsyndromic and is genetically heterogeneous. Nearly 80% of inherited nonsyndromic bilateral sensorineural hearing loss (NBSNHI) is autosomal recessive. Although many causal genes have been identified, most are minor contributors, except for GJB2, which accounts for nearly 50% of all recessive cases of severe to profound congenital NBSNHI in some populations. More than 60% of children with a NBSNHI do not have an identifiable genetic cause. To identify genetic contributors, we genotyped 659 GJB2 mutation negative pediatric probands with NBSNHI and assayed for copy number variants (CNVs). After identifying 8 mild-moderate NBSNHI probands with a Chr15q15.3 deletion encompassing the Stereocilin (STRC) gene amongst this cohort, sequencing of STRC was undertaken in these probands as well as 50 probands and 14 siblings with mild-moderate NBSNHI and 40 probands with moderately severe-profound NBSNHI who were GJB2 mutation negative. The existence of a STRC pseudogene that is 99.6% homologous to the STRC coding region has made the sequencing interpretation complicated. We identified 7/50 probands in the mild-moderate cohort to have biallelic alterations in STRC, not including the 8 previously identified deletions. We also identified 2/40 probands to have biallelic alterations in the moderately severe-profound NBSNHI cohort, notably no large deletions in combination with another variant were found in this cohort. The data suggest that STRC may be a common contributor to NBSNHI among GJB2 mutation negative probands, especially in those with mild to moderate hearing impairment.
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影响因子：
64.8
作者：
Verpy, Elisabeth;Weil, Dominique;Leibovici, Michel;Goodyear, Richard J.;Hamard, Ghislaine;Houdon, Carine;Lefevre, Gaelle M.;Hardelin, Jean-Pierre;Richardson, Guy P.;Avan, Paul;Petit, Christine
通讯作者：
Petit, Christine
影响因子：
4
作者：
Knijnenburg, J.;Oberstein, S. A. J. Lesnik;Szuhai, K.
通讯作者：
Szuhai, K.
影响因子：
56.9
作者：
Sebat, J;Lakshmi, B;Wigler, M
通讯作者：
Wigler, M
影响因子：
4
作者：
Campbell, DA;McHale, DP;Mueller, RF
通讯作者：
Mueller, RF
影响因子：
25
作者：
Petit, Christine;Richardson, Guy P.
通讯作者：
Richardson, Guy P.