Mutations in NOTCH2 in Families with Hajdu-Cheney Syndrome
Mutations in NOTCH2 in Families with Hajdu-Cheney Syndrome
复制标题
DOI：
10.1002/humu.21546
复制
发表时间：
2011-10-01
期刊：
影响因子：
3.9
通讯作者：
Samuels, Mark E.
中科院分区：
文献类型：
--
作者：
Majewski, Jacek;Schwartzentruber, Jeremy A.;Samuels, Mark E.
Hajdu-Cheney综合征(HCS)是一种罕见的遗传性疾病，其特征是骨溶解、末端指骨缩短和全身性骨质疏松。我们组织了一个由7个家系组成的队列，并对选定的一组受影响的患者进行了完整的外显子重新测序。一个编码蛋白质的基因NOTCH2在所有患者及其受影响的家庭成员中携带杂合截断变体。我们的结果复制了最近发表的关于HCS的研究，并进一步支持这一点，认为这是这种疾病的原因基因。总而言之，我们发现了五个新的突变和一个先前报道的突变，所有突变都聚集在该基因的羧基末端附近，这表明了一种等位基因特有的基因型-表型效应，因为据报道，NOTCH2的其他突变会导致一种形式的Alagille综合征。Notch介导的信号转导已知在骨代谢中发挥作用。我们的结果支持Notch通路在治疗骨质疏松症中的潜在治疗作用。HumMutat 32：1114-1117,2011。(C)2011年Wiley-Liss，Inc.
Hajdu-Cheney syndrome (HCS) is a rare genetic disorder whose hallmark is acro-osteolysis, shortening of terminal phalanges, and generalized osteoporosis. We assembled a cohort of seven families with the condition and performed whole exome resequencing on a selected set of affected patients. One protein-coding gene, NOTCH2, carried heterozygous truncating variants in all patients and their affected family members. Our results replicate recently published studies of HCS and further support this as the causal gene for the disorder. In total, we identified five novel and one previously reported mutation, all clustered near the carboxyl terminus of the gene, suggesting an allele specific genotype-phenotype effect since other mutations in NOTCH2 have been reported to cause a form of Alagille syndrome. Notch-mediated signaling is known to play a role in bone metabolism. Our results support a potential therapeutic role for Notch pathways in treatment of osteoporosis. HumMutat 32:1114-1117, 2011. (C) 2011 Wiley-Liss, Inc.