Department of Pediatrics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Misakaenosono Mutsumi Developmental, Medical, and Welfare Center, Isahaya, Japan.
J Hum Genet. 2018 Mar;63(3):387-390. doi: 10.1038/s10038-017-0396-5. Epub 2018 Jan 15.
Takenouchi-Kosaki syndrome (TKS) is a congenital malformation syndrome characterized by severe developmental delay, macrothrombocytopenia, camptodactyly, sensorineural hearing loss, and dysmorphic facial features. Recently, a heterozygous de novo mutation (p.Tyr64Cys) in the CDC42 gene, which encodes a key small GTP-binding protein of the Rho-subfamily, was identified in two unrelated patients with TKS. We herein report a third patient with TKS who had the same heterozygous CDC42 mutation. The phenotype of the patient was very similar to those of the two previously reported patients with TKS; however, she also demonstrated novel clinical manifestations, such as congenital hypothyroidism and immunological disturbance. Thus, despite the heterozygous mutation of CDC42 (p.Tyr64Cys) likely being a hot-spot mutation for TKS, its phenotype may be variable. Further studies and the accumulation of patients with CDC42 mutations are needed to clarify the phenotype in patients with TKS and the pathophysiological roles of the CDC42 mutation.
武井脇综合征（TKS）是一种先天性畸形综合征，其特征为严重的发育迟缓、巨血小板减少症、指（趾）弯曲、感觉神经性听力损失和颜面畸形。最近，在两名无关联的 TKS 患者中发现了 CDC42 基因（编码 Rho 亚家族关键的小 GTP 结合蛋白）的杂合性新生突变（p.Tyr64Cys）。我们在此报告了第三位患有 TKS 的患者，其携带相同的 CDC42 突变。该患者的表型与之前报道的两名 TKS 患者非常相似；然而，她还表现出了新的临床表现，如先天性甲状腺功能减退症和免疫紊乱。因此，尽管 CDC42（p.Tyr64Cys）的杂合性突变可能是 TKS 的热点突变，但它的表型可能存在差异。需要进一步的研究和 CDC42 突变患者的积累，以阐明 TKS 患者的表型以及 CDC42 突变的病理生理作用。
