Application of Molecular Cytogenetics In Microdeletion disease

Microdeletions are a group of chromosomal disorders caused by the deletion of a segment of DNA smaller than 5 megabases. They are inherited as an autosomal dominant trait. Despite the relatively small segment of chromosomal loss affected individuals present with severe and diverse clinical manifestations. The deletion is often beyond the resolution of cytogenetic study and will be missed by routine karyotyping. In cases where any of the microdeletion syndromes are being considered it is necessary to apply more sensitive techniques. Towards this purpose and for the standardization of FISH technique in detection, we proposed to do a prospective study on patients referred for microdeletion syndrome by FISH. In complete clinical, laboratory, radiographical and cytogenetic study of 68 families for microdeletion syndromes, 12 cases were referred with suspicion of having di George syndrome (DGS). Two amniotic fluid samples were received from a multiparous female with a former child with DGS and the other of a fetus with thymus hypoplasia and aortic arch deviation detected in sonography. Cytogenetic study by GTG banding and FISH showed the presence of the critical region on chromosomes 22 for both cases ruling out DGS. From the ten blood samples, one failed to grow. Of the nine remaining samples, in the cases of a two year old girl, both cytogenetic study and FISH detected a deletion of 22q11.2 region confirming the diagnosis of DGS. In the other eight cases, the presence of the critical region on both chromosomes was confirmed by FISH and the diagnosis of DGS was not confirmed. In view of the fact that of 11 cases referred for DGS, only one cases was confirmed to be DGS, and considering that DGS is phenotypically and genotypically heterogeneous, it appears that further clinical workup will lead to better diagnosis.