[Chromosomal location of submicroscopic duplications in patients with neurodevelopmental disorders to identify cases with high risk of familial recurrence]

Abstract

Background and objective: An important proportion of neurodevelopmental disorders (NDDs) results from unbalanced genomic alterations (duplication or deletion). These chromosomal rearrangements may be considered as de novo, despite they arise as a result of a balanced rearrangement not detected in a phenotypically normal parent. Therefore, if the rearrangements are inherited, the recurrence risk and the genetic counseling of these cases change radically. Fluorescence in situ hybridization (FISH) is a technique that allows detecting both balanced and unbalanced rearrangements, identifying also the location of duplicated segments. We tried to locate in the genome the duplicated segments detected in patients with NDDs in order to identify those cases due to inherited rearrangements.

Patients and method: The study was conducted in 13 patients with NDDs and genomic duplications detected by compared genomic hybridization-array (CGH-array). Two approaches of FISH technique were taken: hybridization with painting chromosome probes and with specific probes for each duplication.

Results: In the studied series of 13 patients with duplication, 11 patients were found to carry tandem duplications, one with an intrachromosomal insertional translocation, and another with an interchromosomal insertional translocation. Therefore, 2 of the duplications considered de novo were actually an unbalanced rearrangement inherited from a parent who is a balanced carrier.

Conclusion: The results illustrate the need to characterize by FISH technique the rearrangements that are detected by CGH-array to identify those cases with a high risk of recurrence.

Keywords: Aneusomía segmentaria; Compared genomic hybridization-array; Complex chromosomal rearrangement; Fluorescence in situ hybridization; Hibridación genómica comparada sobre arrays; Hibridación in situ fluorescente; Insertional translocation; Reordenamiento cromosómico complejo; Segmental aneusomy; Traslocación insercional.