The Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV) was used to evaluate the general intellectual ability of the patient when she was 78 months old. The full-scale intelligence quotient was 78, which is at the lower limit of the normal range. The scores of verbal comprehension, perceptual reasoning, working memory, and processing speed subtests were 81, 79, 85, and 79, respectively. Detailed neurological features are shown in Table 1.
To detect disease-causing mutations, genomic DNA was extracted from the peripheral blood samples of the patient and her parents using the Gentra Puregene Blood Kit (Qiagen, Hilden, Germany), according to the manufacturer's protocol. Whole-exome capture was performed using an Agilent SureSelect V6 enrichment capture kit (Agilent Technologies, Inc., Woburn, MA, United States), according to the manufacturer's instructions. The captured library was sequenced using the Illumina HiSeq 2500 System (Illumina, Inc., San Diego, CA, United States). Original sequencing data were assessed using FastQC (version 0.11.2) for quality control. The Burrows Wheeler alignment tool v0.2.10 was used for sequencing data alignment to the Human Reference Genome (NCBI build 37, hg 19). Single-nucleotide variants and small indels were identified using the Genome Analysis Toolkit. All variants were saved in VCF format and uploaded to the Ingenuity Variant Analysis (Ingenuity Systems, Redwood City, CA, United States) and TGex (Translational Genomics Expert) platforms for biological analysis and interpretation, as previously reported. Variants detected by next-generation sequencing were confirmed by Sanger sequencing.
Whole-exome sequencing revealed a novel frame-shift variant, c.2128_2129del, p.Leu710Valfs x 42, in the last exon of SATB1 (NM_001195470.2). Sanger sequencing confirmed the variant as well as the wild-type status of her father and mother (Figure 1B). The control population database (gnomAD) and our local control cohort database did not have reports on the detected variant. The frame-shift variant is classified as a pathogenic variant according to the ACMG guidelines for variant interpretation.