Clinical manifestations in patients with SOS1 mutations range from Noonan syndrome to CFC syndrome
Clinical manifestations in patients with SOS1 mutations range from Noonan syndrome to CFC syndrome
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DOI：
10.1007/s10038-008-0320-0
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发表时间：
2008-09-01
影响因子：
3.5
通讯作者：
Matsubara, Yoichi
中科院分区：
文献类型：
--
作者：
Narumi, Yoko;Aoki, Yoko;Matsubara, Yoichi
努南综合征(NS)和心面部皮肤综合征(CFC)是以心脏缺陷、面部畸形、外胚层异常和智力低下为特征的常染色体显性遗传性疾病。NS和CFC综合征在临床上有显著的重叠，但外胚层异常和智力低下在CFC综合征中更常见。在NS患者中发现了PTPN11和KRAS突变，在CFC综合征患者中发现了KRAS、BRAF和MAP2K1/2突变，从而确立了RAS/MAPK通路在人类发育中的新作用。最近，在NS患者中也发现了Seven less基因之子(SOS1)的突变。为了阐明SOS1突变患者的临床谱系，我们分析了24例NS患者，其中包括一个三代家族中的3名患者，以及30名没有PTPN11、KRAS、HRAS、BRAF和MAP2K1/2(MEK1/2)突变的CFC综合征患者。我们在四名NS患者中发现了两个SOS1突变，其中包括上述三代家族中的三名患者。在具有CFC型的患者中，在一名CFC型患者和两名同时具有NS和CFC型的患者中发现了三个突变，包括一个新的三个氨基酸插入。这三名患者表现出外胚层异常，如卷发、稀疏的眉毛和干燥的皮肤，其中两名患者表现出智力低下。我们的结果表明，SOS1突变的患者范围从NS到CFC综合征。
Noonan syndrome (NS) and cardio-facio-cutaneous (CFC) syndrome are autosomal dominant disorders characterized by heart defects, facial dysmorphism, ectodermal abnormalities, and mental retardation. There is a significant clinical overlap between NS and CFC syndrome, but ectodermal abnormalities and mental retardation are more frequent in CFC syndrome. Mutations in PTPN11 and KRAS have been identified in patients with NS and those in KRAS, BRAF and MAP2K1/2 have been identified in patients with CFC syndrome, establishing a new role of the RAS/MAPK pathway in human development. Recently, mutations in the son of sevenless gene (SOS1) have also been identified in patients with NS. To clarify the clinical spectrum of patients with SOS1 mutations, we analyzed 24 patients with NS, including 3 patients in a three-generation family, and 30 patients with CFC syndrome without PTPN11, KRAS, HRAS, BRAF, and MAP2K1/2 (MEK1/2) mutations. We identified two SOS1 mutations in four NS patients, including three patients in the above-mentioned three-generation family. In the patients with a CFC phenotype, three mutations, including a novel three amino-acid insertion, were identified in one CFC patient and two patients with both NS and CFC phenotypes. These three patients exhibited ectodermal abnormalities, such as curly hair, sparse eyebrows, and dry skin, and two of them showed mental retardation. Our results suggest that patients with SOS1 mutations range from NS to CFC syndrome.