Biallelic mutation of Protocadherin-21 (PCDH21) causes retinal degeneration in humans
Biallelic mutation of Protocadherin-21 (PCDH21) causes retinal degeneration in humans
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发表时间：
2008-05
期刊：
影响因子：
2.2
通讯作者：
R. Henderson;Zheng Li;Mai M. Abd El Aziz;D. Mackay;M. A. Eljinini;Marwan Zeidan;A. Moore;S. Bhattacharya;A. Webster
中科院分区：
文献类型：
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作者：
R. Henderson;Zheng Li;Mai M. Abd El Aziz;D. Mackay;M. A. Eljinini;Marwan Zeidan;A. Moore;S. Bhattacharya;A. Webster
目的描述与原钙粘蛋白-21（procadherin-21，PCDH-21）基因突变相关的常染色体隐性视网膜营养不良（retinal dystrophy）家系的临床表现和突变情况。方法对一个常染色体隐性遗传性视网膜营养不良家系的两个成员进行全基因组扫描，并确定了遗传上相同的区域。定位候选基因进行鉴定和测序。所有患者都进行了详细的眼科检查，包括视网膜电图和视网膜成像。结果两个家系的患者在染色体10 q的一个重叠区表现出完全相同的纯合性。对候选基因PCDH 21的测序结果显示，在282条对照染色体中未检测到c.337delG（p.G113AfsX1）和c.1459delG（p.G487GfsX20）两个单独的纯合单碱基缺失。这两个家庭的受影响成员在青少年后期首次报告夜盲症，并保持良好的中央视力，直到他们30多岁。所有先证者均无色觉。眼底外观包括黄斑和周边视网膜出现特征性圆形色素上皮萎缩斑块。结论光感受器特异性基因PCDH 21的双等位基因突变导致人类隐性视网膜变性。
Purpose To describe the clinical findings and mutations in affected members of two families with an autosomal recessive retinal dystrophy associated with mutations in the protocadherin-21 (PCDH21) gene. Methods A full genome scan of members of two consanguineous families segregating an autosomal recessive retinal dystrophy was performed and regions identical by descent identified. Positional candidate genes were identified and sequenced. All patients had a detailed ophthalmic examination, including electroretinography and retinal imaging. Results Affected members of both families showed identical homozygosity for an overlapping region of chromosome 10q. Sequencing of a candidate gene, PCDH21, showed two separate homozygous single-base deletions, c.337delG (p.G113AfsX1) and c.1459delG (p.G487GfsX20), which were not detected in 282 control chromosomes. Affected members of the two families first reported nyctalopia in late teenage years and retained good central vision until their late 30s. No color vision was detected in any proband. The fundus appearance included the later development of characteristic circular patches of pigment epithelial atrophy at the macula and in the peripheral retina. Conclusions Biallelic mutations in the photoreceptor-specific gene PCDH21 cause recessive retinal degeneration in humans.