X-linked late-onset sensorineural deafness caused by a deletion involving OA1 and a novel gene containing WD-40 repeats
X-linked late-onset sensorineural deafness caused by a deletion involving OA1 and a novel gene containing WD-40 repeats
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DOI：
10.1086/302408
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发表时间：
1999-06-01
影响因子：
9.8
通讯作者：
Borsani, G
中科院分区：
文献类型：
--
作者：
Bassi, MT;Ramesar, RS;Borsani, G
我们在Xp22.3基因组区域发现了一个新的基因，transducin（beta）-like 1（TBL 1），它与WD-40-repeat蛋白家族的成员具有很高的同源性。该基因包含18个外显子：跨越与眼白化病基因（OA 1）端粒侧相邻的150 kb基因组区域。然而，与OA 1不同，TBL 1是从端粒转录的。到着丝粒。北方分析表明，TBL 1基因在大肠杆菌中广泛表达，有两个大小相似的转录本，大小分别为2.1 kb和6.0 kb。开放阅读框编码526个氨基酸的蛋白质，其显示在C-末端结构域中存在六个β-转导素重复序列（WD-40基序）。与已知的G蛋白和其他WD-40重复蛋白的β-亚基的同源性仅限于WD-40基序。基因组分析表明，在携带Xp22.3末端缺失的患者中，该基因部分或全部缺失，这些患者所共有的连续基因-综合征表型的复杂性取决于参与缺失的已知疾病基因的数量;有趣的是，一名携带涉及TBL 1和OA 1的3 ′部分的微间质缺失的患者显示与X连锁晚期-感音神经性耳聋我们推测TBL 1参与了眼白化病伴迟发性感音神经性耳聋表型的发病机制。
We have, identified a novel gene, transducin (beta)-like 1 (TBL1), in the Xp22.3 genomic region, that shows high homology with members of the WD-40-repeat protein family. The gene Contains 18 exons: spanning similar to 150 kb of the genomic region adjacent to the ocular albinism gene (OA1) on the telomeric side. However, unlike OA1, TBL1 is' transcribed from telomere. to centromere. Northern analysis indicates that TBL1 is ubiquitously expressed, with two transcripts of similar to 2.1 kb and 6.0 kb. The open reading frame encodes a 526-amino acid protein, which shows the presence of six beta-transducin repeats (WD-40 motif) in the C-terminal domain. The homology with known beta-subunits of G proteins and other WD-40-repeat containing proteins-is restricted to the WD-40 motif. Genomic analysis revealed that the gene is either partly or entirely deleted in patients carrying Xp22.3 terminal deletions, The complexity of the contiguous gene-syndrome phenotype shared by these patients depends on the number of known disease genes involved in the deletions; Interestingly, one patient carrying a microinterstitial deletion involving the 3' portion of both TBL1 and OA1 shows the OA1 phenotype associated with X-linked late-onset sensorineural deafness. We postulate an involvement of TBL1 in the pathogenesis of the ocular albinism with late-onset sensorineural deafness phenotype.