caa a22 4500 445824263 CHVBK 20180317145254.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s00246-011-0024-7 doi (NATIONALLICENCE)springer-10.1007/s00246-011-0024-7 Familial Nonsyndromic Patent Ductus Arteriosus Caused by Mutations in TFAP2B [Elektronische Daten] [Yi-Wei Chen, Wu Zhao, Zhi-Fang Zhang, Qihua Fu, Jie Shen, Zhen Zhang, Wei Ji, Jian Wang, Fen Li] Patent ductus arteriosus (PDA) is a common congenital heart disease that develops soon after birth when the arterial duct does not remodel. Mutations in TFAP2B, which encodes a neural crest-derived transcription factor, can cause Char syndrome, characterized by PDA, facial dysmorphism, and skeletal abnormalities of the hand. The TFAP2B mutations result in a great amount of phenotypic variability, and a novel TFAP2B mutation has been found in patients with nonsyndromic PDA. Therefore, this study investigated whether TFAP2B mutations can cause familial nonsyndromic PDA. Clinical data and peripheral blood specimens were collected from two kindreds (A and B) and from a cohort of 100 unrelated subjects with PDA. Kindred A spanned three generations, in which 5 of the 16 individuals had PDA, and kindred B spanned three generations, in which 2 of the 13 individuals had PDA. The study enrolled 100 unrelated healthy individuals as control subjects. Polymerase chain reaction (PCR) was used to amplify seven exons and flanking introns of the TFAP2B gene. A few exons of the TFAP2B gene were amplified using reverse transcription polymerase chain reaction (RT-PCR), and direct forward and reverse sequencing of the PCR products was performed. The acquired sequences were aligned with those in GenBank by using a basic local alignment search tool (BLAST). The following two types of mutations were identified in TFAP2B: c.601+5G>A and c.435_438delCCGG. The mutation c.601+5G>A was detected in the affected members of kindred A. Nested PCR showed a splice junction in intron 3 and a 61-bp deletion in exon 3. The mutation c.435_438delCCGG, found in the affected members of kindred B, was caused by a four-base deletion in exon 2, which in turn caused a frame shift that resulted in the formation of a premature stop codon, p.Arg145Argfsx45. None of these mutations was detected in the unaffected members of the kindred or in the control group. Furthermore, two novel single-nucleotide polymorphisms (SNPs), c.1-34G>A and c.539+62G>C, were detected in the introns. The variant c.1-34G>A was identified 34bp upstream of the transcription initiation site in the TFAP2B gene. Significant differences in the prevalence of the alleles G and A were observed in the control subjects and PDA patients (Z=−2.513, P=0.012). The study identified that another variant was c.539+62G>C but that the frequency of this variant was similar between the control subjects and the PDA patients (Z=−0.332, P=0.74). The TFAP2B mutations may be associated with isolated nonsyndromic, hereditary PDA in Chinese families. The authors propose that a TFAP2B mutation should be considered a risk factor for isolated PDA. However, the detailed genetic mechanism underlying nonsyndromic the PDA-causing TFAP2B mutation is yet to be elucidated. Springer Science+Business Media, LLC, 2011 Congenital heart disease nationallicence Genetic mutation nationallicence Patent ductus arteriosus nationallicence Transcription factor AP-2B nationallicence Chen Yi-Wei Department of Cardiology, Shanghai Children's Medical Center Affiliated With Shanghai Jiaotong University School of Medicine, 200127, Shanghai, People's Republic of China aut Zhao Wu Department of Pediatric Cardiology, First Hospital Affiliated to BengBu Medical College, 233004, BengBu, People's Republic of China aut Zhang Zhi-Fang Department of Cardiology, Shanghai Children's Medical Center Affiliated With Shanghai Jiaotong University School of Medicine, 200127, Shanghai, People's Republic of China aut Fu Qihua Research Division of Birth Defects, Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, 200127, Shanghai, People's Republic of China aut Shen Jie Department of Cardiology, Shanghai Children's Hospital Affiliated to Shanghai Jiaotong University, 200040, Shanghai, People's Republic of China aut Zhang Zhen Department of Cardiology, Shanghai Children's Medical Center Affiliated With Shanghai Jiaotong University School of Medicine, 200127, Shanghai, People's Republic of China aut Ji Wei Department of Cardiology, Shanghai Children's Medical Center Affiliated With Shanghai Jiaotong University School of Medicine, 200127, Shanghai, People's Republic of China aut Wang Jian Research Division of Birth Defects, Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, 200127, Shanghai, People's Republic of China aut Li Fen Department of Cardiology, Shanghai Children's Medical Center Affiliated With Shanghai Jiaotong University School of Medicine, 200127, Shanghai, People's Republic of China aut Pediatric Cardiology Springer-Verlag 32/7(2011-10-01), 958-965 0172-0643 32:7<958 2011 32 246 https://doi.org/10.1007/s00246-011-0024-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00246-011-0024-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chen Yi-Wei Department of Cardiology, Shanghai Children's Medical Center Affiliated With Shanghai Jiaotong University School of Medicine, 200127, Shanghai, People's Republic of China aut NATIONALLICENCE 700 1- Zhao Wu Department of Pediatric Cardiology, First Hospital Affiliated to BengBu Medical College, 233004, BengBu, People's Republic of China aut NATIONALLICENCE 700 1- Zhang Zhi-Fang Department of Cardiology, Shanghai Children's Medical Center Affiliated With Shanghai Jiaotong University School of Medicine, 200127, Shanghai, People's Republic of China aut NATIONALLICENCE 700 1- Fu Qihua Research Division of Birth Defects, Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, 200127, Shanghai, People's Republic of China aut NATIONALLICENCE 700 1- Shen Jie Department of Cardiology, Shanghai Children's Hospital Affiliated to Shanghai Jiaotong University, 200040, Shanghai, People's Republic of China aut NATIONALLICENCE 700 1- Zhang Zhen Department of Cardiology, Shanghai Children's Medical Center Affiliated With Shanghai Jiaotong University School of Medicine, 200127, Shanghai, People's Republic of China aut NATIONALLICENCE 700 1- Ji Wei Department of Cardiology, Shanghai Children's Medical Center Affiliated With Shanghai Jiaotong University School of Medicine, 200127, Shanghai, People's Republic of China aut NATIONALLICENCE 700 1- Wang Jian Research Division of Birth Defects, Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, 200127, Shanghai, People's Republic of China aut NATIONALLICENCE 700 1- Li Fen Department of Cardiology, Shanghai Children's Medical Center Affiliated With Shanghai Jiaotong University School of Medicine, 200127, Shanghai, People's Republic of China aut NATIONALLICENCE 773 0- Pediatric Cardiology Springer-Verlag 32/7(2011-10-01), 958-965 0172-0643 32:7<958 2011 32 246 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer