Background: Microdeletions at 17q21.31 have recently been shown to cause a novel syndrome. Here we identify the reciprocal 17q21.31 duplication syndrome in four patients.
Method: Patients with the 17q21.31 duplication were indentified by screening a large cohort of patients (n=13070) with mental retardation and congenital malformation by CGH microarray. Parental origin was investigated in three patients by quantitative PCR and microsatellite genotyping.
Results: In three cases it was possible to show that duplication arose de novo. Intellectual skills range from normal to mild mental retardation. Patients are characterized by poor social interaction, with relationship difficulties, reminiscent of autistic spectrum disorders. Other features are rather variable with no striking common phenotypic features. Parental origin was investigated for 3 patients. In all cases duplication was of maternal origin either through interchromosomal (2 cases) or interchromatid (1 case) rearrangement. The three mothers are all carriers of the inverted H2 haplotype emphasizing the role of local genomic architecture alteration as a predisposing factor for this duplication.
Conclusion: Autistic features observed in our patients suggest that genes in the duplicated interval should be considered as candidates for disorders in the autistic spectrum. Other phenotypic observations are rather variable or aspecific. This adds 17q21.31 duplications to a growing group of recently identified genomic disorders with variable penetrance and expressivity.