Allele-specific impairment of GJB2 expression by GJB6 deletion del(GJB6-D13S1854).
Allele-specific impairment of GJB2 expression by GJB6 deletion del(GJB6-D13S1854).
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DOI：
10.1371/journal.pone.0021665
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Schrijver I
中科院分区：
文献类型：
--
作者：
Rodriguez-Paris J;Tamayo ML;Gelvez N;Schrijver I
编码连接蛋白26的GJB2基因突变是先天性非综合征性感音神经性听力损失的常见原因。两个大缺失del（GJB6- d13s1830）和del（GJB6- d13s1854）截断GJB6（连接蛋白30），导致这些缺失纯合或复合杂合的个体听力损失，或者GJB2中一个这样的缺失和突变。最近，我们已经证明del（GJB6-D13S1830）缺失导致听力损失是由于等位基因特异性缺乏GJB2 mRNA表达，而不是像之前假设的那样是基因遗传的结果。在目前的研究中，我们研究了较小的del（GJB6-D13S1854）缺失，它在转录水平上破坏GJB2的表达，其方式与更常见的del（GJB6-D13S1830）缺失相似。有趣的是，在这种缺失的存在下，GJB2的表达保持在最低限度，但可重复存在。在GJB2突变和del（GJB6-D13S1854）复合杂合的3个先证者中，采用逆转录酶PCR和限制性消化法评估GJB2的相对等位基因特异性表达。每个个体携带不同的GJB2序列变体。这3个个体都表达了突变GJB2等位基因与del的反式表达（GJB6-D13S1854），但GJB2等位基因与缺失的顺式表达几乎不存在。我们的研究清楚地证实了这样的假设，即del（GJB6- d13s1854）与更大、更常见的del（GJB6- d13s1830）相似，它去除了GJB6上游假定的顺式调控元件(s)，缩小了定位区域。
Mutations in the GJB2 gene, which encodes connexin 26, are a frequent cause of congenital non-syndromic sensorineural hearing loss. Two large deletions, del(GJB6-D13S1830) and del(GJB6-D13S1854), which truncate GJB6 (connexin 30), cause hearing loss in individuals homozygous, or compound heterozygous for these deletions or one such deletion and a mutation in GJB2. Recently, we have demonstrated that the del(GJB6-D13S1830) deletion contributes to hearing loss due to an allele-specific lack of GJB2 mRNA expression and not as a result of digenic inheritance, as was postulated earlier. In the current study we investigated the smaller del(GJB6-D13S1854) deletion, which disrupts the expression of GJB2 at the transcriptional level in a manner similar to the more common del(GJB6-D13S1830) deletion. Interestingly, in the presence of this deletion, GJB2 expression remains minimally but reproducibly present. The relative allele-specific expression of GJB2 was assessed by reverse-transcriptase PCR and restriction digestions in three probands who were compound heterozygous for a GJB2 mutation and del(GJB6-D13S1854). Each individual carried a different sequence variant in GJB2. All three individuals expressed the mutated GJB2 allele in trans with del(GJB6-D13S1854), but expression of the GJB2 allele in cis with the deletion was almost absent. Our study clearly corroborates the hypothesis that the del(GJB6-D13S1854), similar to the larger and more common del(GJB6-D13S1830), removes (a) putative cis-regulatory element(s) upstream of GJB6 and narrows down the region of location.
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影响因子：
4
作者：
del Castillo, FJ;Rodríguez-Ballesteros, M;del Castillo, I
通讯作者：
del Castillo, I
DOI：
10.1073/pnas.0800831105
发表时间：
2008-12-02
影响因子：
11.1
作者：
Ortolano, Saida;Di Pasquale, Giovanni;Chiorini, John A.
通讯作者：
Chiorini, John A.
影响因子：
158.5
作者：
del Castillo, I;Villamar, M;Moreno, F
通讯作者：
Moreno, F
DOI：
10.1016/s0006-291x(03)01166-5
发表时间：
2003-07-25
影响因子：
3.1
作者：
Ahmad, S;Chen, SP;Lin, X
通讯作者：
Lin, X
影响因子：
5.2
作者：
Pallares-Ruiz, N;Blanchet, P;Roux, AF
通讯作者：
Roux, AF