Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype
Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype
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DOI：
10.1038/ng2113
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发表时间：
2007-09-01
期刊：
影响因子：
30.8
通讯作者：
Legius, Eric
中科院分区：
文献类型：
--
作者：
Brems, Hilde;Chmara, Magdalena;Legius, Eric
我们报告了一种新发现的常染色体显性遗传人类疾病中SPRED 1的生殖细胞功能缺失突变。SPRED 1是SPROUTY/ SPRED蛋白家族（1）的成员，其作为RAS-RAF相互作用和促分裂原活化蛋白激酶（MAPK）信号传导的负调节剂（2）。该疾病的临床特征与神经纤维瘤病1型相似，包括多发性咖啡Au斑、腋窝雀斑和大头畸形。来自咖啡- Au- lait斑的黑素细胞显示，除了生殖系SPRED 1突变外，野生型SPRED 1等位基因中的获得性体细胞突变，表明在该综合征中需要完全的SPRED 1失活以产生咖啡- Au- lait斑.这种疾病是最近表征的由编码RAS-MAPK途径关键组分的基因突变引起的表型重叠综合征组的另一个成员（3，4）。据我们所知，这是人类疾病中SPRY（SPROUTY）/ SPRED基因家族突变的首次报道。
We report germline loss- of- function mutations in SPRED1 in a newly identified autosomal dominant human disorder. SPRED1 is a member of the SPROUTY/ SPRED family(1) of proteins that act as negative regulators of RAS- RAF interaction and mitogen-activated protein kinase ( MAPK) signaling(2). The clinical features of the reported disorder resemble those of neurofibromatosis type 1 and consist of multiple cafe - au- lait spots, axillary freckling and macrocephaly. Melanocytes from a cafe - au- lait spot showed, in addition to the germline SPRED1 mutation, an acquired somatic mutation in the wild- type SPRED1 allele, indicating that complete SPRED1 inactivation is needed to generate a cafe - au- lait spot in this syndrome. This disorder is yet another member of the recently characterized group of phenotypically overlapping syndromes caused by mutations in the genes encoding key components of the RAS- MAPK pathway(3,4). To our knowledge, this is the first report of mutations in the SPRY ( SPROUTY)/ SPRED family of genes in human disease.