Congenital anomalies are a leading cause of infant mortality in European countries. A considerable proportion of these anomalies are caused by chromosome translocations. Through translocation-based positional cloning, an ever-growing number of candidate genes have been identified, but the mechanism by which the constitutional translocations lead to the phenotype is largely unknown. 

 

By investigating 9 translocations, we confirmed that most breakpoints lie in intergenic regions introducing a disruption in genomic architecture, namely in cis-acting elements, rather than directly affecting the "conventional" expression unit of a gene. In 2009, Kleinjan and Coutinho introduced the term "cis-ruption disorders" to describe this group of genetic disorders.

 

During the development of this project we studied two translocation-associated "cis-ruption" disorders:

• Syndromic form of Peter's Anomaly, associated with t(11;18)

• Split-hand Split-foot malformation, associated with chromosome translocations involving the 2q14.1 and 2q14.2 regions

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This project was funded by Portuguese Fundação para a Ciência e a Tecnologia (FCT)  PTDC/SAU-GMG/118140/2010

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