The emerging microduplication 3q13.31: Expanding the genotype-phenotype correlations of the reciprocal microdeletion 3q13.31 syndrome

Abstract

Microdeletion and microduplication syndromes are well-known causes of developmental delay and/or malformations of differing severity. It was recently reported that a microdeletion at the 3q13.31 locus is associated with a new syndrome combining developmental delay, postnatal overgrowth and dysmorphic features. However, the reciprocal microduplication has only been described in a few case reports displaying some clinical features of the microdeletion syndrome. Here, we report on a female infant with a 3.34 Mb microduplication of the 3q13.2q13.31 region inherited from her mother. The infant presented with severe intellectual disability, learning difficulties, intrauterine and postnatal growth retardation and skeletal particularities but no dysmorphic traits. This microduplication encompassed the previously described shortest region of overlap, which contains five genes (DRD3, ZNF80, TIGIT, MIR568 and ZBTB20). We reviewed the phenotypes described in the literature on microduplications and in the well-characterized 3q13.31 microdeletion syndrome. In agreement with the literature data, DRD3 and ZBTB20 appear to be strong candidate genes for neurodevelopmental defects and growth retardation. Lastly, we consider the putative mechanism of this rearrangement, which may involve a particular kind of nonallelic homologous recombination of human endogenous retrovirus elements.