- Balanced translocations and abnormal phenotypes : what is the relationship ?
Apparently balanced chromosomal rearrangements (translocations or inversions) associated to an abnormal phenotype have allowed to clone numerous disease genes. The activity of the cytogenetics laboratory of the Timone children's hospital in Marseilles or the collaborations that we have established with foreign cytogenetics labs gave us several such balanced rearrangements associated with abnormal phenotypes, namely mental retardation. These rearrangements can be associated to a clinical symptomatology likely corresponding to a monogenic disease, a syndromic condition or to more complex clinical pictures. In each instance, mental retardation can be present. We are performing physical mapping to localize the breakpoints, identify the molecular mechanism likely responsible for the abnormal phenotype and the mental retardation (deletion or duplication at the breakpoint or disruption of one or several genes).
Here are some examples of chromosomal rearrangements studied in our lab :
inv(X)(p22;q13) that lead to the cloning of the KIAA2022 gene in two patients with severe mental retardation.
t(X;21) that lead to the cloning of the KLF8 gene in a female patient with moderate MR.
t(13;15) that lead to the cloning of a new gene (currently studied) in a patient with moderate MR.
t(10;13) that lead to the cloning of a new gene (currently studied) in a patient with severe MR.
t(5;18) in a patient with moderate MR that we are studying with the laboratory of André Mégarbané in Lebanon.