title: A unique TBX5 microdeletion with microinsertion detected in patient with Holt-Oram syndrome.
abstract: 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.
authors.affiliation: General Perinatal Medical Center, Shikoku Medical Center for Children and Adults, Zentsuji, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Morine
authors.affiliation: Department of Human Genetics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.|Student Lab, Tokushima University Faculty of Medicine, Tokushima, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kohmoto
authors.affiliation: Department of Human Genetics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Masuda
authors.affiliation: Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan.
authors.forename: Hidehito
authors.initials: H
authors.lastname: Inagaki
authors.affiliation: Department of Human Genetics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.|Student Lab, Tokushima University Faculty of Medicine, Tokushima, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Stress Science, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Naruto
authors.affiliation: Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurahashi
authors.affiliation: General Perinatal Medical Center, Shikoku Medical Center for Children and Adults, Zentsuji, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Maeda
authors.affiliation: Department of Human Genetics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Issei
authors.initials: I
authors.lastname: Imoto
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000328:Adult; D005260:Female; D017353:Gene Deletion; D006330:Heart Defects, Congenital / Q000235:genetics* / Q000473:pathology; D006344:Heart Septal Defects, Atrial / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D038061:Lower Extremity Deformities, Congenital / Q000235:genetics* / Q000473:pathology; D016254:Mutagenesis, Insertional / Q000235:genetics*; D011379:Prognosis; D020825:T-Box Domain Proteins / Q000235:genetics*; D038062:Upper Extremity Deformities, Congenital / Q000235:genetics* / Q000473:pathology
chemical_list: D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5
keywords: Holt–Oram syndrome; TBX5; error‐prone DNA polymerase; microindel