Single nucleotide polymorphism array analysis uncovers a large, novel duplication in Xq13.1 in a floppy infant syndrome patient

•A large, novel duplication in Xq13.1 was found in a floppy infant syndrome(FIS) patient.•This duplication might induce an impairment of central and peripheral nervous system development.•This duplication might cause the symptoms of FIS.•Single nucleotide polymorphism array could be recommended as the first option for genetic diagnosis of FIS. To identify candidate genes for the clinical diagnosis of floppy infant syndrome (FIS) using single nucleotide polymorphism (SNP) array in a specific FIS family. SNP array analysis of the whole chromosome copy number was performed in the proband (III1). Multiple polymerase chain reaction (PCR) combined with denaturing high-performance liquid chromatography (DHPLC) was used to validate the array data. A large 5.818182 Mb duplication (Xq13.1: 67987646–73805828), which encompasses 66 known genes, was found in III1. The start and end points of the duplication were confirmed with an SNP array. Duplicated genes with potential roles in central and/or peripheral nervous system development (HDAC8, PHKA1, TAF1, DLG3, KIF4A, IGBP1, PJA1, and SLC16A2) were confirmed by multiple PCR-DHPLC in III1. The patient’s mother and grandmother carry duplications in these eight genes, but only on one X chromosome, while the patient’s aunt does not carry any of the duplications. Based on the location of the eight candidate genes in Xq13.1, the large duplication found by SNP array does indeed exist and is predicted to be both novel and pathogenic. Moreover, we recommend SNP array as the first option for genetic diagnosis of both large-scale and rare/complicated diseases, such as FIS.