Genetic Analysis of Oral-Facial-Digital Syndrome

The customized panel for oral–facial–digital (OFD) syndrome included five genes: C2CD3, CPLANE1, DDX59, OFD1, and TCTN3. Baits for the OFD gene panel and whole-exome sequencing (WES), which targeted on comprehensive medical exomes, were purchased from Agilent. Both the targeted sequencing library and the WES library for patient 33 were constructed using the Agilent SureSelect clinical research exome kit, except that the hybrid captures were performed using different baits as described above. Sequencing was conducted on a NextSeq550 sequencer (Illumina) with 100 bp paired-end reads. The DNA sequence was aligned to the human reference genome (UCSC hg19). We built a sequence processing pipeline for analyzing both the targeted gene panel and the WES data by incorporating two commercial software, CLC biomedical genomic workbench from QIAGEN and AlamutBatch from Interactive Biosoftware. The evaluation and the classification of variants were performed following the American College of Medical Genetics (ACMG) recommendations (Richards et al., 2015 (link)).