A unique TBX5 microdeletion with microinsertion detected in patient with Holt-Oram syndrome

Mikio Morine, Tomohiro Kohmoto, Kiyoshi Masuda, Hidehito Inagaki, Miki Watanabe, Takuya Naruto, Hiroki Kurahashi, Kazuhisa Maeda, Issei Imoto

Research output: Contribution to journalArticle


Holt-Oram syndrome (HOS) is an autosomal dominant condition characterized by upper limb and congenital heart defects and caused by numerous germline mutations of TBX5 producing preterminal stop codons. Here, we report on a novel and unusual heterozygous TBX5 microdeletion with microinsertion (microindel) mutation (c.627delinsGTGACTCAGGAAACGCTTTCCTGA), which is predicted to synthesize a truncated TBX5 protein, detected in a sporadic patient with clinical features of HOS prenatally diagnosed by ultrasonography. This uncommon and relatively large inserted sequence contains sequences derived from nearby but not adjacent templates on both sense and antisense strands, suggesting two possible models, which require no repeat sequences, causing this complex microindel through the bypass of large DNA adducts via an error-prone DNA polymerase-mediated translesion synthesis.

Original languageEnglish
Pages (from-to)3192-3196
Number of pages5
JournalAmerican Journal of Medical Genetics, Part A
Issue number12
Publication statusPublished - 01-12-2015


All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Morine, M., Kohmoto, T., Masuda, K., Inagaki, H., Watanabe, M., Naruto, T., Kurahashi, H., Maeda, K., & Imoto, I. (2015). A unique TBX5 microdeletion with microinsertion detected in patient with Holt-Oram syndrome. American Journal of Medical Genetics, Part A, 167(12), 3192-3196. https://doi.org/10.1002/ajmg.a.37359