A genotypic and phenotypic analysis of four unrelated Chinese patients with Pitt–Hopkins syndrome

Abstract Background Pitt–Hopkins syndrome (PTHS) is a rare genetic condition caused by a mutation in the transcription Factor 4 ( TCF4 ) gene and characterized by its unique clinical presentations. At present, there is an incomplete understanding of the possible TCF4 mutations and their downstream consequences, and no reliable treatment exists for patients with PTHS. Elucidating the variations in TCF4 occurring in PTHS could lead to new treatment ideas. Case presentation We described the clinical and genetic characteristics of four Chinese patients with PTHS. Genetic mutations related to central nervous system (CNS) disorders were identified via high-throughput sequencing. The patient’s mutations were subsequently confirmed with Sanger sequencing. Most patients had facial features typical of PTHS; however, Patient 2 demonstrated poor auricle shape. Each patient presented with differing levels of delayed development and intellectual impairment. The patients showed a splice site mutation in intron 15 of TCF4 (c.1452 + 3A > G), a frameshift mutation in exon 18 of TCF4 (c.1942delA), and two missense mutations in exon 19 of TCF4 (c. 2147C > T and c.2026A > G). Conclusions We discovered four new TCF4 mutations in Chinese children with PTHS. To our knowledge, the c.2026A > G and c.1942delA mutations have not yet been reported. The detection of these mutations can help accurately diagnose PTHS early, especially in patients whose clinical symptoms are not obvious. Exploring the genotype and phenotype of individuals with PTHS, will enrich our understanding and guide further research into the role of TCH4 .