Mutations In Congenital Heart Disease Also Linked to Neurodevelopmental Abnormalities

Jonathan Kaltman, MD Chief, Heart Development and Structural Diseases Branch Division of Cardiovascular Sciences National Heart, Lung, and Blood Institute

Dr. Kaltman

MedicalResearch.com Interview with:
Jonathan Kaltman, MD

Chief, Heart Development and Structural Diseases Branch
Division of Cardiovascular Sciences
National Heart, Lung, and Blood Institute

Medical Research: What are the main findings?

Dr. Kaltman:  Congenital heart disease (CHD) is the most common birth defect but the cause for most defects is unknown.  Surgery and clinical care of patients with congenital heart disease has improved survival but now we are learning that many patients have neurodevelopmental abnormalities, including learning disability and attention/behavioral issues.

Medical Research:  What are the main findings?

  • Using exome sequencing we found that patients with  congenital heart disease have a substantial number of de novo mutations.  This finding is especially strong in patients with CHD and another structural birth defect and/or neurodevelopmental abnormalities.
  • Many of the genes identified are known to be expressed in both the heart and the brain, suggesting a single mutation may contribute to both congenital heart disease and neurodevelopmental abnormalities.

Medical Research: What should clinicians and patients take away from your report?

Dr. Kaltman:  Defects in certain genes result in a very high risk for developing neurodevelopmental abnormalities.  If these findings are replicated and refined we might be able to develop a genetic test that could identify patients at high risk for developing neurodevelopmental abnormalities, enabling clinicians to target these patients for surveillance and early intervention.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Kaltman:

  • We need to replicate and refine these findings in order to determine if they can be made into a clinically actionable test.
  • These findings are helping to identify new pathways that are critical to heart and brain development improving our basic knowledge of how the human body develops and will also provide insight into the causes of various birth defects.

Citation:

Homsy, S. Zaidi, Y. Shen, J. S. Ware, K. E. Samocha, K. J. Karczewski, S. R. DePalma, D. McKean, H. Wakimoto, J. Gorham, S. C. Jin, J. Deanfield, A. Giardini, G. A. Porter, R. Kim, K. Bilguvar, F. Lopez-Giraldez, I. Tikhonova, S. Mane, A. Romano-Adesman, H. Qi, B. Vardarajan, L. Ma, M. Daly, A. E. Roberts, M. W. Russell, S. Mital, J. W. Newburger, J. W. Gaynor, R. E. Breitbart, I. Iossifov, M. Ronemus, S. J. Sanders, J. R. Kaltman, J. G. Seidman, M. Brueckner, B. D. Gelb, E. Goldmuntz, R. P. Lifton, C. E. Seidman, W. K. Chung. De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies. Science, 2015; 350 (6265): 1262 DOI:10.1126/science.aac9396

Jonathan Kaltman, MD (2015). Mutations In Congenital Heart Disease Also Linked to Neurodevelopmental Abnormalities MedicalResearch.com

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