Neuronal migration genes and a familial translocation t (3;17): candidate genes implicated in the phenotype

Abstract

Background: While Miller-Dieker syndrome critical region deletions are well known delineated anomalies, submicroscopic duplications in this region have recently emerged as a new distinctive syndrome. So far, only few cases have been described overlapping 17p13.3 duplications. Methods: In this study, we report on clinical and cytogenetic characterization of two new cases involving 17p13.3 and 3p26 chromosomal regions in two sisters with familial history of lissencephaly. Fluorescent In Situ Hybridization and array Comparative Genomic Hybridization were performed. Results: A deletion including the critical region of the Miller-Dieker syndrome of at least 2,9 Mb and a duplication of at least 3,6 Mb on the short arm of chromosome 3 were highlighted in one case. The opposite rearrangements, 17p13.3 duplication and 3p deletion, were observed in the second case. This double chromosomal aberration is the result of an adjacent 1:1 meiotic segregation of a maternal reciprocal translocation t(3,17)(p26.2;p13.3). Conclusions: 17p13.3 and 3p26 deletions have a clear range of phenotypic features while duplications still have an uncertain clinical significance. However, we could suggest that regardless of the type of the rearrangement, the gene dosage and interactions of CNTN4, CNTN6 and CHL1 in the 3p26 and PAFAH1B1, YWHAE in 17p13.3 could result in different clinical spectrums.

A new case of 17p13.3p13.1 microduplication resulted from unbalanced translocation: clinical and molecular cytogenetic characterization

“…To date, just a few patients with duplication of region pter → p13.1 of chromosome 17 have been described. In all cases, the diagnosed genomic imbalance was a consequence of malsegregation of the parent's reciprocal translocation [16][17][18][19]. The patients had a complex phenotype due to a combination of partial trisomy of the short arm of chromosome 17 and partial monosomy of another chromosome involved in the rearrangement.…”