title: Exome sequencing reveals novel IRXI mutation in congenital heart disease.
abstract: Genetic variation in specific transcription factors during heart formation may lead to congenital heart disease (CHD) or even miscarriage. The aim of the present study was to identify CHD‑associated genes using next generation sequencing (NGS). The whole exome DNA sequence was obtained from a stillborn fetus diagnosed with tricuspid atresia and complete transposition of the great arteries using high‑throughput sequencing methods. Subsequently, genetic variants of CHD‑associated genes were selected and verified in 215 non‑syndromic CHD patients and 249 healthy control subjects using polymerase chain reaction combined with Sanger sequencing. Genetic variants of previously reported CHD‑inducing genes, such as cysteine rich with EGF like domains 1 and cbp/p300‑interacting transactivator with Glu/Asp rich carboxy‑terminal domain 2, were discovered through the NGS analysis. In addition, a novel non‑synonymous mutation of the iroquois homeobox 1 (IRX1) gene (p.Gln240Glu) was identified. A total of three non‑synonymous mutations (p.Gln240Glu, p.Ser298Asn and p.Ala381Glu) of the IRX1 gene were verified in 215 non‑syndromic CHD patients, but not in 249 healthy volunteers. The results demonstrated that NGS is a powerful tool to study the etiology of CHD. In addition, the results suggest that genetic variants of the IRX1 gene may contribute to the pathogenesis of CHD.
authors.affiliation: Department of Genetics, National Research Institute for Family Planning, Haidian, Beijing 100081, P.R. China.
authors.forename: Changlong
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Genetics, National Research Institute for Family Planning, Haidian, Beijing 100081, P.R. China.
authors.forename: Qidi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Surgery, Union Hospital, Fujian Medical University, Fuzhou, Fujian 350001, P.R. China.
authors.forename: Liping
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Genetics, National Research Institute for Family Planning, Haidian, Beijing 100081, P.R. China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Genetics, National Research Institute for Family Planning, Haidian, Beijing 100081, P.R. China.
authors.forename: Xiao Fang
authors.initials: XF
authors.lastname: Cao
authors.affiliation: Department of Genetics, National Research Institute for Family Planning, Haidian, Beijing 100081, P.R. China.
authors.forename: Lisha
authors.initials: L
authors.lastname: An
authors.affiliation: Department of Genetics, National Research Institute for Family Planning, Haidian, Beijing 100081, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Genetics, National Research Institute for Family Planning, Haidian, Beijing 100081, P.R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Du
authors.affiliation: Department of Genetics, National Research Institute for Family Planning, Haidian, Beijing 100081, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Genetics, National Research Institute for Family Planning, Haidian, Beijing 100081, P.R. China.
authors.forename: Cailing
authors.initials: C
authors.lastname: Lu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006330:Heart Defects, Congenital / Q000235:genetics* / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D018398:Homeodomain Proteins; C501591:IRX1 protein, human; D014157:Transcription Factors