Morine Mikio, Kohmoto Tomohiro, Masuda Kiyoshi, Inagaki Hidehito, Watanabe Miki, Naruto Takuya, Kurahashi Hiroki, Maeda Kazuhisa, Imoto Issei
General Perinatal Medical Center, Shikoku Medical Center for Children and Adults, Zentsuji, Japan.
Department of Human Genetics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Am J Med Genet A. 2015 Dec;167A(12):3192-6. doi: 10.1002/ajmg.a.37359. Epub 2015 Sep 28.
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.
霍尔特-奥拉姆综合征（HOS）是一种常染色体显性疾病，其特征为上肢和先天性心脏缺陷，由产生终末前终止密码子的TBX5基因众多种系突变所致。在此，我们报告了一例新的、罕见的杂合性TBX5微小缺失伴微小插入（微缺失插入，microindel）突变（c.627delinsGTGACTCAGGAAACGCTTTCCTGA），预计该突变会合成截短的TBX5蛋白，此突变在一名产前经超声诊断具有HOS临床特征的散发性患者中被检测到。这个不常见且相对较大的插入序列包含来自有义链和反义链上附近但不相邻模板的序列，提示了两种可能的模型，这两种模型不需要重复序列，通过易出错的DNA聚合酶介导的跨损伤合成绕过大型DNA加合物，从而导致这种复杂的微缺失插入。
