The effect of p.Arg25Cys alteration in NKX2-5 on conotruncal heart anomalies: mutation or polymorphism?
Heterozygous mutations in the NKX2-5 gene of patients with various congenital heart defects have been reported. Most of the congenital heart defects associated with the mutations in the NKX2-5 gene are conotruncal heart anomalies, primarily the tetralogy of Fallot. In this study, the authors screened 72 Turkish children with conotruncal heart anomalies and 185 healthy control subjects to find the NKX2-5 alterations. They found one previously documented NKX2-5 missense alteration, heterozygous c.73C>T (p.Arg25Cys), in a 10-year-old boy with tetralogy of Fallot. The same heterozygous alteration was found also in the patient's healthy father and in two unrelated persons in the healthy control group. The current study shows for the first time the presence of p.Arg25Cys in healthy control subjects other than African Americans. These results show that no genetic support exists for the pathogenecity of this alteration, although a previous in vitro study and theoretical predictions suggest a structural/functional difference in the altered protein region.
Akçaboy
M I
MI
Division of Pediatric Genetics, Ankara University School of Medicine, Birlik Mah. 65. Sok. No: 20/7, Cankaya, Ankara 06610, Turkey.
Cengiz
F B
FB
Inceoğlu
B
B
Uçar
T
T
Atalay
S
S
Tutar
E
E
Tekin
M
M
D001120:Arginine / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003545:Cysteine / Q000235:genetics; D004310:Double Outlet Right Ventricle / Q000235:genetics; D005260:Female; D006330:Heart Defects, Congenital / Q000235:genetics*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D018633:Pulmonary Atresia / Q000235:genetics; D013771:Tetralogy of Fallot / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014188:Transposition of Great Vessels / Q000235:genetics; D014339:Truncus Arteriosus, Persistent / Q000235:genetics
D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D014157:Transcription Factors; D001120:Arginine; D003545:Cysteine