Research Laboratory, KK Women's and Children's Hospital, Singapore.
SingHealth Duke-NUS Academic Clinical Programme, Singapore.
Am J Med Genet A. 2022 Jul;188(7):2135-2138. doi: 10.1002/ajmg.a.62724. Epub 2022 Mar 15.
Pathogenic variants in NOTCH2 which encodes a single-pass transmembrane protein have been identified as a cause of several autosomal dominant congenital disorders. In particular, truncating mutations in exon 34 have been found in patients with skeletal abnormalities and dysmorphic features. We describe a patient with a de novo variant in NOTCH2 who displayed features of both Hajdu-Cheney syndrome (HJCYS) and serpentine fibula-polycystic kidney syndrome (SFPKS). The recurrent nonsense variant in exon 34 has been reported in seven other patients with syndromic presentations, making it the most common pathogenic variant for NOTCH2 in congenital disorders. In addition to the core features of HJCYS and SFPKS, there was a gastrointestinal tract malformation of an imperforate anus which has not been reported in patients with pathogenic variants in NOTCH2.
编码单次跨膜蛋白的 NOTCH2 中的致病变异已被确定为几种常染色体显性先天性疾病的病因。特别是，在骨骼异常和发育不良特征的患者中发现了 34 号外显子的截断突变。我们描述了一名患有 NOTCH2 新生变异的患者，其表现出 Hajdu-Cheney 综合征（HJCYS）和蛇形腓骨多囊肾病综合征（SFPKS）的特征。该外显子 34 中的重复无义变异已在其他七名有综合征表现的患者中报道，使其成为先天性疾病中 NOTCH2 最常见的致病变异。除了 HJCYS 和 SFPKS 的核心特征外，还有肛门闭锁的消化道畸形，在 NOTCH2 致病变异的患者中尚未报道过这种畸形。
