title: Genetic and functional analysis of the TBX3 gene promoter in indirect inguinal hernia.
abstract: Inguinal hernia is a common developmental disease in children and most cases are indirect inguinal hernia (IIH). Genetic factors have been suggested to play important roles in IIH. Although IIH has been observed in several human syndromes, genetic causes and molecular mechanisms for IIH remain unknown. TBX3 is a member of the T-box family of transcription factors that are essential to the embryonic development. Human studies and animal experiments have demonstrated that TBX3 is required for the development of the heart, limbs, mammary glands and other tissues and organs. TBX3 gene expression has been detected in human fibroblast and tissues of abdominal wall. We speculated that TBX3 may be involved in the IIH formation. Since TBX3 activity is highly dosage-sensitive, a TBX3 gene promoter was genetically and functionally analyzed in IIH patients and ethnic-matched controls in this study. One heterozygous deletion variant (g.4820_4821del) was identified in one IIH patient, but in none of controls. The variant significantly decreased TBX3 gene promoter activities, likely by creating a binding site for sex-determining region Y (SRY), mobility group transcription factor. One heterozygous insertion variant (g.3913_3914ins) was only found in one control, which did not affect TBX3 gene promoter activities. Taken together, TBX3 gene variants may contribute to IIH as a rare risk factor by reducing TBX3 levels.
authors.affiliation: Division of Interventional Radiology, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China.
authors.forename: Zhongqing
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250000, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Tian
authors.affiliation: Division of Interventional Radiology, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China.
authors.forename: Haihua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China.
authors.forename: Xianyun
authors.initials: X
authors.lastname: Qin
authors.affiliation: Division of Pediatric Surgery, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China.
authors.forename: Qining
authors.initials: Q
authors.lastname: Xing
authors.affiliation: Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China.
authors.forename: Shuchao
authors.initials: S
authors.lastname: Pang
authors.affiliation: Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China; Shandong Provincial Sino-US Cooperation Research Center for Translational Medicine, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D017353:Gene Deletion; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006552:Hernia, Inguinal / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D051876:Sex-Determining Region Y Protein / Q000235:genetics; D020825:T-Box Domain Proteins / Q000378:metabolism*
chemical_list: C491387:JDP2 protein, human; D012097:Repressor Proteins; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; D020825:T-Box Domain Proteins; C106884:TBX3 protein, human
keywords: DNA sequence variants; Genetics; Indirect inguinal hernia; Promoter; TBX3