Familial 9q33q34 microduplication in siblings with developmental disorders and macrocephaly

Abstract

Because several genes responsible for epileptic encephalopathy are located on the 9q33q34 region, patients with chromosomal deletions of this region often show intractable epilepsy and neurodevelopmental disability. Contrary to these findings, chromosomal duplications of this region have never been reported previously. We identified a first case of 9q33q34 microduplications in siblings associated with developmental disorders and macrocephaly. Their mother was a mosaic carrier of this duplication. Duplicated regions involved STXBP1; the gene related to epileptic encephalopathy. Neurological features including developmental delay and macrocephaly observed in the present siblings may be derived from the extra-copy of STXBP1.

Keywords: Autistic features; Fluorescence in-situ hybridization (FISH); Next-generation sequencing; Triplosensitivity score; eXome Hidden Markov Model (XHMM).