Current address: Northern Genetic Service, Institute of Human Genetics, Newcastle University, International Centre for Life, Newcastle upon Tyne, UK.
New mutations in ZFPM2/FOG2 gene in tetralogy of Fallot and double outlet right ventricle
Version of Record online: 2 AUG 2010
© 2010 John Wiley & Sons A/S
Special Issue: Exome Sequencing
Volume 80, Issue 2, pages 184–190, August 2011
How to Cite
De Luca, A., Sarkozy, A., Ferese, R., Consoli, F., Lepri, F., Dentici, M., Vergara, P., De Zorzi, A., Versacci, P., Digilio, M., Marino, B. and Dallapiccola, B. (2011), New mutations in ZFPM2/FOG2 gene in tetralogy of Fallot and double outlet right ventricle. Clinical Genetics, 80: 184–190. doi: 10.1111/j.1399-0004.2010.01523.x
- Issue online: 12 JUL 2011
- Version of Record online: 2 AUG 2010
- Accepted manuscript online: 2 AUG 2010 12:00AM EST
- Received 8 May 2010, revised and accepted for publication 27 July 2010
- congenital heart defects;
- conotruncal defects;
- double outlet right ventricle;
- tetralogy of Fallot;
De Luca A, Sarkozy A, Ferese R, Consoli F, Lepri F, Dentici ML, Vergara P, De Zorzi A, Versacci P, Digilio MC, Marino B, Dallapiccola B. New mutations in ZFPM2/FOG2 gene in tetralogy of Fallot and double outlet right ventricle.
Conotruncal defects (CTDs) represent 15–20% of all congenital heart defects. Mutations in a number of genes have been associated with CTD in humans and animal models. We investigated the occurrence and the prevalence of GATA4, NKX2.5, ZFPM2/FOG2, GDF1, and ISLET1 gene mutations in a large cohort of individuals with CTD, including tetralogy of Fallot with or without pulmonary atresia (TOF, 178 patients), double outlet right ventricle (DORV, 13 patients), and truncus arteriosus (11 patients). Denaturing high-performance liquid chromatography (DHPLC) analysis followed by bidirectional sequencing disclosed no putative pathogenic mutation in GATA4, ISLET1, and GDF1 genes. Two novel (Ile227Val, Met544Ile) and one previously reported (Glu30Gly) possibly pathogenic missense variants were identified in the ZFPM2/FOG2 gene in 3 sporadic patients of 202 (1.5%) with CTD, including 1 of 178 (0.6%) with TOF and 2 of 13 (15.4%) with DORV. Mutation analysis also detected one known missense change (Arg25Cys) in NKX2.5 gene in two (1.1%) sporadic patients with TOF. These sequence alterations were found to be absent in 500 population-matched controls. In conclusion, the present results (i) indicate and confirm that mutations in the GATA4, GDF1, and ISLET1 genes are not major determinants in the pathogenesis of TOF, (ii) provide supportive evidence of an association between ZFPM2/FOG2 gene and TOF/DORV, and (iii) provide additional examples of the possible contribution of the Arg25Cys change in the NKX2.5 to a small number of TOF cases.