Yamada Mamiko, Funato Michinori, Kondo Goro, Suzuki Hisato, Uehara Tomoko, Takenouchi Toshiki, Sakamoto Yoshiaki, Kosaki Kenjiro
Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan.
Department of Pediatrics, National Hospital Organization Nagara Medical Center, Gifu, Japan.
Congenit Anom (Kyoto). 2021 Nov;61(6):226-230. doi: 10.1111/cga.12435. Epub 2021 Jul 11.
Craniosynostosis is caused by abnormalities of multiple signaling pathways, including excessive RAS signaling. Recently, a truncating variant in ETS2 repressor factor (ERF), a negative transcriptional regulator of the RAS pathway, was shown to be associated with craniosynostosis. Here, we report a 10-year-old male patient with a heterozygous nonsense mutation, p.Arg183*, in ERF who exhibited craniosynostosis with Noonan syndrome-like phenotypes. In consideration that loss-of-function variants in ERF would result in excessive RAS signaling and RASopathy phenotypes, we propose that ERF may represent a causative gene for Noonan syndrome. Since preceding studies on ERF mutations dealt with patients who were ascertained because of craniosynostosis, further studies are needed to evaluate whether patients with variants in ERF can present with Noonan syndrome-like features without craniosynostosis.
颅缝早闭由多种信号通路异常引起，包括RAS信号过度激活。最近，RAS通路的负性转录调节因子ETS2抑制因子（ERF）中的一个截短变异体被证明与颅缝早闭有关。在此，我们报告一名10岁男性患者，其ERF基因存在杂合性无义突变p.Arg183*，表现为颅缝早闭并伴有努南综合征样表型。鉴于ERF功能丧失变异会导致RAS信号过度激活和RAS病表型，我们提出ERF可能是努南综合征的致病基因。由于之前关于ERF突变的研究涉及的患者是因颅缝早闭而确诊的，因此需要进一步研究来评估ERF变异患者是否可在无颅缝早闭的情况下表现出努南综合征样特征。
