Novel phenotypic feature in a patient with a recurrent NOTCH2 nonsense mutation. Issue 7 (15th March 2022)

• Record Type: Journal Article
• Authors: Tan, Ene‐Choo; Lai, Angeline H. M.; Brett, Maggie S. Y.
• Is Part Of: American journal of medical genetics. Volume 188:Issue 7(2022)
• Page Start: 2135
• Page End: 2138
• Publication Date: 2022-03-15
• Subjects: global developmental delay -- Hajdu–Cheney syndrome -- imperforate anus -- neurodevelopmental disorder -- serpentine fibula‐polycystic kidney syndrome -- truncating variant; Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.62724
• Languages: English
• ISSNs: 1552-4825

Abstract

Abstract: 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 .