Rare partial trisomy and tetrasomy of 15q11-q13 associated with developmental delay and autism spectrum disorder

Abstract

Background: Small supernumerary marker chromosomes (sSMCs), are additional abnormal chromosomes, which can’t be detected accurately by conventional cytogenetic analysis. Duplication of chromosome 15 might be account for 50% of the total sSMCs and usually leads to mental retardation, structural malformation, behavioral problems and epilepsy.Case presentation: An 11-month-old infant with an sSMC was referred to our clinic because of developmental retardation and autism spectrum disorder. After several months of rehabilitation treatment, the progress of motor development was obvious, but the consciousness was still far from satisfied. High-resolution karyotype analysis, multiplex ligation-dependent probe amplification and copy number variation sequencing (CNV-Seq) were conducted to confirm the identity of the sSMC. A bisatellited dicentric sSMC was observed clearly in high-resolution karyotype analysis and a 10.16-Mb duplication of 15q11.1q13.2 together with a 1.84-Mb duplication of 15q13.2q13.3 was showed by CNV-Seq in the proband. It suggested that the molecular cytogenetic karyotype was 47, XY,+inv dup(15)(pter/q13::q13/pter) which identify the proband was 15q duplication syndrome (dup15q). Furthermore, the clinical symptoms of the proband mostly fit this disease which is characterized by hypotonia motor delays, autism spectrum disorder (ASD), and intellectual disability.Conclusion: Our research indicates that CNV-seq is a robust, sensitive and economical way for diagnosis of dup15q and related disorders.