Editors' ChoiceDown Syndrome

Divide and Conquer: Teasing Out the Cause of Heart Defects in Down Syndrome

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Science Translational Medicine  20 Apr 2011:
Vol. 3, Issue 79, pp. 79ec54
DOI: 10.1126/scitranslmed.3002506

Prenatal testing gives pregnant women important information about the developing fetus; it checks for a variety of abnormalities, including the aneuploidy that results in Down syndrome. Qualitative karyotype analysis can identify Down syndrome, which is caused by three copies of chromosome 21; however, it cannot provide detailed information about the constellation of different phenotypes associated with Down syndrome. A study from Liu et al. has planted the seed of paradigm change for prenatal testing for this condition.

The researchers examined three regions on mouse chromosomes that are conserved with regions associated with Down syndrome on human chromosome 21: Mmu10, Mmu16, and Mmu17. They found that duplications on Mmu16 were associated with Down syndrome–related congenital heart defects. On the basis of this finding, they then developed two mouse models to investigate gene-level abnormalities associated with heart malformations. Using these models, the researchers determined that triplication of an individual region on Mmu 16 (Tiam1-Knj) led to Down syndrome–associated heart conditions.

These data shed light on how individual genetic mutations may contribute to the different conditions that can manifest in individuals with Down syndrome. This type of nuanced information carries the clinical potential to help better inform the major life decisions that pregnant patients must make after prenatal genetic testing.

C. Liu et al., Genetic analysis of Down syndrome-associated heart defects in mice. Hum. Genet. 10 April 2011 (10.1007/s00439-011-0980-2). [PubMed]

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