BACKGROUND: Congenital heart disease (CHD) is the most common birth defect and affects nearly 1% of newborns. The aetiology of CHD is largely unknown and only a small percentage can be assigned to environmental risk factors such as maternal diseases or exposure to mutagenic agents during pregnancy. Chromosomal imbalances have been identified in many forms of syndromic CHD, but very little is known about the impact of DNA copy number changes in non-syndromic CHD. METHOD: A sub-megabase resolution array comparative genome hybridisation (CGH) screen was carried out on 105 patients with CHD as the sole abnormality at the time of diagnosis. RESULTS: There were 18 chromosomal changes detected, which do not coincide with common DNA copy number variants, including one de novo deletion, two de novo duplications and eight familial copy number variations (one deletion and seven duplications). CONCLUSIONS: Our data show that submicroscopic deletions and duplications play an important role in the aetiology of this condition, either as direct causes or as genetic risk factors for CHD. These findings have immediate consequences for genetic counselling and should pave the way for the elucidation of the pathogenetic mechanisms underlying CHD.
BACKGROUND:Congenital heart disease (CHD) is the most common birth defect and affects nearly 1% of newborns. The aetiology of CHD is largely unknown and only a small percentage can be assigned to environmental risk factors such as maternal diseases or exposure to mutagenic agents during pregnancy. Chromosomal imbalances have been identified in many forms of syndromic CHD, but very little is known about the impact of DNA copy number changes in non-syndromic CHD. METHOD: A sub-megabase resolution array comparative genome hybridisation (CGH) screen was carried out on 105 patients with CHD as the sole abnormality at the time of diagnosis. RESULTS: There were 18 chromosomal changes detected, which do not coincide with common DNA copy number variants, including one de novo deletion, two de novo duplications and eight familial copy number variations (one deletion and seven duplications). CONCLUSIONS: Our data show that submicroscopic deletions and duplications play an important role in the aetiology of this condition, either as direct causes or as genetic risk factors for CHD. These findings have immediate consequences for genetic counselling and should pave the way for the elucidation of the pathogenetic mechanisms underlying CHD.
Authors: Jill A Rosenfeld; Ryan N Traylor; G Bradley Schaefer; Elizabeth W McPherson; Blake C Ballif; Eva Klopocki; Stefan Mundlos; Lisa G Shaffer; Arthur S Aylsworth Journal: Eur J Hum Genet Date: 2012-02-08 Impact factor: 4.246
Authors: Abigail S Carey; Li Liang; Jonathan Edwards; Tracy Brandt; Hui Mei; Andrew J Sharp; Daphne T Hsu; Jane W Newburger; Richard G Ohye; Wendy K Chung; Mark W Russell; Jill A Rosenfeld; Lisa G Shaffer; Michael K Parides; Lisa Edelmann; Bruce D Gelb Journal: Circ Cardiovasc Genet Date: 2013-09-10
Authors: Elizabeth Goldmuntz; Prasuna Paluru; Joseph Glessner; Hakon Hakonarson; Jaclyn A Biegel; Peter S White; Xiaowu Gai; Tamim H Shaikh Journal: Congenit Heart Dis Date: 2011-10-20 Impact factor: 2.007
Authors: Elisabeth E Mlynarski; Michael Xie; Deanne Taylor; Molly B Sheridan; Tingwei Guo; Silvia E Racedo; Donna M McDonald-McGinn; Eva W C Chow; Jacob Vorstman; Ann Swillen; Koen Devriendt; Jeroen Breckpot; Maria Cristina Digilio; Bruno Marino; Bruno Dallapiccola; Nicole Philip; Tony J Simon; Amy E Roberts; Małgorzata Piotrowicz; Carrie E Bearden; Stephan Eliez; Doron Gothelf; Karlene Coleman; Wendy R Kates; Marcella Devoto; Elaine Zackai; Damian Heine-Suñer; Elizabeth Goldmuntz; Anne S Bassett; Bernice E Morrow; Beverly S Emanuel Journal: Hum Genet Date: 2016-01-07 Impact factor: 4.132