A complex intragenic rearrangement of ERCC8 in Chinese siblings with Cockayne syndrome.
A complex intragenic rearrangement of ERCC8 in Chinese siblings with Cockayne syndrome.
复制标题
患有科凯恩综合征的中国兄弟姐妹中 ERCC8 的复杂基因内重排
DOI：
10.1038/srep44271
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发表时间：
2017-03-23
影响因子：
4.6
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Xie H;Li X;Peng J;Chen Q;Gao Z;Song X;Li W;Xiao J;Li C;Zhang T;Gusella JF;Zhong J;Chen X
Cockayne综合征是一种常染色体隐性遗传疾病，主要特征是出生后生长障碍和进行性神经功能障碍，主要是由于ERCC 6和ERCC 8突变。在这里，我们报告我们的诊断经验，在一个中国家庭的两个病人怀疑在临床上有科凯恩综合征。使用多种分子技术，包括全外显子组测序、阵列比较基因组杂交和定量聚合酶链反应，我们鉴定了母本剪接变体（chr 5：60195556，NM_000082：c.618-2A > G）和父本复杂缺失/倒位/缺失重排去除ERCC 8外显子4的复合杂合性，证实了这两个受试者的疑似发病机制。断点处的微同源性（TAA和AGCT）表明微同源性介导的FoSTeS事件参与了这种复杂的ERCC 8重排。这种诊断经验说明了高通量基因组技术结合详细的表型评估在临床遗传诊断中的价值。
Cockayne syndrome is an autosomal recessive disorder principally characterized by postnatal growth failure and progressive neurological dysfunction, due primarily to mutations in ERCC6 and ERCC8. Here, we report our diagnostic experience for two patients in a Chinese family suspected on clinical grounds to have Cockayne syndrome. Using multiple molecular techniques, including whole exome sequencing, array comparative genomic hybridization and quantitative polymerase chain reaction, we identified compound heterozygosity for a maternal splicing variant (chr5:60195556, NM_000082:c.618-2A > G) and a paternal complex deletion/inversion/deletion rearrangement removing exon 4 of ERCC8, confirming the suspected pathogenesis in these two subjects. Microhomology (TAA and AGCT) at the breakpoints indicated that microhomology-mediated FoSTeS events were involved in this complex ERCC8 rearrangement. This diagnostic experience illustrates the value of high-throughput genomic technologies combined with detailed phenotypic assessment in clinical genetic diagnosis.