Mutation analysis of the SHOC2 gene in Noonan-like syndrome and in hematologic malignancies
Mutation analysis of the SHOC2 gene in Noonan-like syndrome and in hematologic malignancies
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DOI：
10.1038/jhg.2010.116
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发表时间：
2010-12-01
影响因子：
3.5
通讯作者：
Matsubara, Yoichi
中科院分区：
文献类型：
--
作者：
Komatsuzaki, Shoko;Aoki, Yoko;Matsubara, Yoichi
努南综合征是一种常染色体显性遗传疾病，以畸形、蹼颈、心脏畸形、身材矮小和隐睾为特征。它显示与Costello综合征和心-面-皮肤（CFC）综合征的表型重叠。努南综合征和相关疾病是由RAS/MAPK通路中编码分子的基因的种系突变引起的。最近，SHOC 2中的功能获得性突变p.S2G已被鉴定为一种以生长期毛发疏松为特征的努南样综合征的病因。为了了解SHOC 2突变对努南综合征和相关疾病临床表现的影响，我们分析了92例努南综合征和相关疾病患者的SHOC 2，这些患者未表现出PTPN 11、KRAS、HRAS、BRAF、MAP 2K 1/2、SOS 1或RAF 1突变。我们在8名患者中发现了先前确定的p.S2G突变。我们建立了一个快速检测系统，通过熔解曲线分析来鉴定p.S2G突变，这将是一个有用的工具，以筛选明显常见的突变。所有p.S2G突变患者均表现为身材矮小、头发稀疏和过敏性皮肤。突变阳性的患者中有6人表现出严重的智力迟钝和容易拔毛，1人表现出白细胞增多。在82例白血病患者的白血病细胞中未发现SHOC 2突变。这些结果表明，SHOC 2突变阳性患者的临床表现与典型努南综合征或CFC综合征患者的临床表现部分重叠，并表明SHOC 2突变阳性患者的毛发生长期易拔/松散是独特的。Journal of Human Genetics（2010）55，801-809; doi：10.1038/jhg.2010.116; 2010年9月30日在线发表
Noonan syndrome is an autosomal dominant disease characterized by dysmorphic features, webbed neck, cardiac anomalies, short stature and cryptorchidism. It shows phenotypic overlap with Costello syndrome and cardio-facio-cutaneous (CFC) syndrome. Noonan syndrome and related disorders are caused by germline mutations in genes encoding molecules in the RAS/MAPK pathway. Recently, a gain-of-function mutation in SHOC2, p.S2G, has been identified as causative for a type of Noonan-like syndrome characterized by the presence of loose anagen hair. In order to understand the contribution of SHOC2 mutations to the clinical manifestations of Noonan syndrome and related disorders, we analyzed SHOC2 in 92 patients with Noonan syndrome and related disorders who did not exhibit PTPN11, KRAS, HRAS, BRAF, MAP2K1/2, SOS1 or RAF1 mutations. We found the previously identified p.S2G mutation in eight of our patients. We developed a rapid detection system to identify the p.S2G mutation using melting curve analysis, which will be a useful tool to screen for the apparently common mutation. All the patients with the p.S2G mutation showed short stature, sparse hair and atopic skin. Six of the mutation-positive patients showed severe mental retardation and easily pluckable hair, and one showed leukocytosis. No SHOC2 mutations were identified in leukemia cells from 82 leukemia patients. These results suggest that clinical manifestations in SHOC2 mutation-positive patients partially overlap with those in patients with typical Noonan or CFC syndrome and show that easily pluckable/loose anagen hair is distinctive in SHOC2 mutation-positive patients. Journal of Human Genetics (2010) 55, 801-809; doi:10.1038/jhg.2010.116; published online 30 September 2010