Familial intellectual disability as a result of a derivative chromosome 22 originating from a balanced translocation (3;22) in a four generation family

Background: Balanced reciprocal translocation is usually an exchange of two terminal segments from different chromosomes without phenotypic effect on the carrier while leading to increased risk of generating unbalanced gametes. Here we describe a four-generation family in Shandong province of China with at least three patients sharing severe intellectual disability and developmental delay resulting from a derivative chromosome 22 originating from a balanced translocation (3;22) involving chromosomes 3q28q29 and 22q13.3. Methods: The proband and his relatives were detected by using karyotyping, chromosome microarray analysis, fluorescent in situ hybridization and real-time qPCR. Results: The proband, a 17 month-old boy, presented with severe intellectual disability, developmental delay, specific facial features and special posture of hands. Pedigree analysis showed that there were at least three affected patients. The proband and other two living patients manifested similar phenotypes and were identified to have identically abnormal cytogenetic result with an unbalanced translocation of 9.0 Mb duplication at 3q28q29 and a 1.7Mb microdeletion at 22q13.3 by karyotyping and chromosome microarray analysis. His father and other five relatives had a balanced translocation of 3q and 22q. Fluorescence in situ hybridization and real-time qPCR definitely validated the results. Conclusions: The abnormal phenotypes of the proband and his two living members in four generations of the family confirmed the 3q duplication and 22q13.3 deletion inherited from familial balanced translocation. This is the first report of familial balanced reciprocal translocation involving chromosomes 3q28q29 and 22q13.3 segregating through four generations.