Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis
Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis
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DOI：
10.1038/ng.778
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发表时间：
2011-04-01
期刊：
影响因子：
30.8
通讯作者：
Le Caignec, Cedric
中科院分区：
文献类型：
--
作者：
Isidor, Bertrand;Lindenbaum, Pierre;Le Caignec, Cedric
Hajdu-Cheney综合征是一种罕见的常染色体显性遗传性骨骼疾病，伴有面部畸形、骨质疏松和肢端骨质溶解。我们对6名患有这种综合征的无关个体的外显子组进行了测序，并在其中5名患者中鉴定了NOTCH 2的杂合无义突变和移码突变。所有突变都聚集在基因的最后一个编码外显子上，这表明突变的mRNA产物逃避了无义介导的衰变，并且所产生的截短的NOTCH 2蛋白以功能获得的方式起作用。
Hajdu-Cheney syndrome is a rare autosomal dominant skeletal disorder with facial anomalies, osteoporosis and acro-osteolysis. We sequenced the exomes of six unrelated individuals with this syndrome and identified heterozygous nonsense and frameshift mutations in NOTCH2 in five of them. All mutations cluster to the last coding exon of the gene, suggesting that the mutant mRNA products escape nonsense-mediated decay and that the resulting truncated NOTCH2 proteins act in a gain-of-function manner.