Genetic mutation analysis in Japanese patients with non-syndromic congenital heart disease.
Congenital heart disease (CHD) is the most common birth defect occurring in humans and some transcriptional factors have been identified as causative. However, additional mutation analysis of these genes is necessary to develop effective diagnostic and medical treatment methods. We conducted sequence analysis of the coding regions of NKX2.5, GATA4, TBX1, TBX5, TBX20, CFC1 and ZIC3 in 111 Japanese patients with non-syndromic CHD and 9 of their relatives. All patient samples were also analyzed by multiplex ligation-dependent probe amplification using probes involved in chromosome deletion related to CHD. Five novel variations of TBX5, GATA4 and TBX20 were detected in 6 of the patients, whereas none were found in 200 controls. The TBX5 variation p.Pro108Thr, located in the T-box domain, was identified in a patient with tricuspid atresia, an exon-intron boundary variation of GATA4 (IVS4+5G>A) was detected in a Tetralogy of Fallot patient and an 8p23 microdeletion was detected in one patient with atrioventricular septal defect and psychomotor delay. A total of seven non-synonymous polymorphisms were found in the patients and controls. Accumulation of novel variations of genes involving the cardiac development may be required for better understanding of CHD.
Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan.|Department of Medical Genetics, National Cerebral and Cardiovascular Center, Suita, Japan.
Akiko
A
Yoshida
Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan.|Department of Medical Genetics, National Cerebral and Cardiovascular Center, Suita, Japan.|Department of Molecular Pathophysiology, Osaka University Graduate School of Pharmaceutical Sciences, Suita, Japan.
Hiroko
H
Morisaki
Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan.|Department of Molecular Pathophysiology, Osaka University Graduate School of Pharmaceutical Sciences, Suita, Japan.
Mai
M
Nakaji
Department of Pediatric Cardiology, National Cerebral and Cardiovascular Center, Suita, Japan.
Masataka
M
Kitano
Division of Cardiology, National Center for Child Health and Development, Tokyo, Japan.
Ki-Sung
KS
Kim
Department of Pediatric Cardiology, Fukuoka Children's Hospital Medical Center, Fukuoka, Japan.
Koichi
K
Sagawa
Department of Pediatric Cardiology, Fukuoka Children's Hospital Medical Center, Fukuoka, Japan.
Shiro
S
Ishikawa
Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Ichiro
I
Satokata
Department of Pediatrics, Mie University Graduate School of Medicine, Tsu, Japan.
Yoshihide
Y
Mitani
Division of Cardiology, National Center for Child Health and Development, Tokyo, Japan.
Hitoshi
H
Kato
Department of Pediatric Cardiology and Nephrology, Kyoto Prefectural University of Medicine Graduate School of Medical Sciences, Kyoto, Japan.
Kenji
K
Hamaoka
Department of Pediatric Cardiology, National Cerebral and Cardiovascular Center, Suita, Japan.
Shigeyuki
S
Echigo
Department of Pediatric Cardiology, National Cerebral and Cardiovascular Center, Suita, Japan.
Isao
I
Shiraishi
Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan.|Department of Medical Genetics, National Cerebral and Cardiovascular Center, Suita, Japan.|Department of Molecular Pathophysiology, Osaka University Graduate School of Pharmaceutical Sciences, Suita, Japan.
Takayuki
T
Morisaki
D002872:Chromosome Deletion; D004252:DNA Mutational Analysis; D050991:GATA4 Transcription Factor / Q000235:genetics; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D007564:Japan; D009154:Mutation; D011110:Polymorphism, Genetic; D020825:T-Box Domain Proteins / Q000235:genetics
D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5; C420984:TBX20 protein, human