HRAS中的从头生殖系突变导致Costello综合征,>95%的突变导致Costello综合征影响氨基酸位置12(p。Gly12)或13(第Gly13)。我们报道了一名患者的从头错义突变导致HRAS密码子146的氨基酸变化,c.436G>C:p。Ala146Pro,表现出微妙的畸形特征,未能茁壮成长,全球发育迟缓,和肥厚性梗阻性心肌病。在<1%的Costello综合征患者中观察到影响密码子146的突变。从文献检索,仅有另外两名患者报告了涉及同一位置的突变.我们总结并更新了他们的发现,和讨论的证据表明,这些不太明显的Costello综合征的患者可能不一定运行更良性的临床过程。
De novo germline mutations in HRAS cause Costello syndrome, with >95% of the mutations causing Costello syndrome affecting amino acid position 12 (p.Gly12) or 13 (p.Gly13). We report on a patient with de novo missense mutation causing an amino acid change at codon 146 of HRAS, c.436G > C:p.Ala146Pro, who presented with subtle dysmorphic features, failure to thrive, global developmental delay, and hypertrophic obstructive cardiomyopathy. Mutations affecting codon 146 are observed in <1% of patients with Costello syndrome. From literature search, there were only two other patients reported with mutations involving the same location. We summarized and updated their findings, and discussed evidence to show that these patients with less obvious signs of Costello syndrome may not necessarily run a more benign clinical course.