Abstract:

Objective ·To explore the pathogenic gene and the mutation type of a family with X-linked spondyloepiphyseal dysplasia tarda (SEDT). Methods ·Genomic DNA was extracted from the peripheral blood of 6 members of a SEDT family. Clearseq hereditary disease kit was applied to target pathogenic regions related to the rare hereditary diseases in the genomic sample of the proband, and then high-throughput sequencing and deletion of high-frequency variants were preformed. Copy number variant (CNV) was analyzed by using exome-hidden Markov model (XHMM). Real-time quantitative PCR was performed to further analyze the copy numbers of the gene deletion fragment in the 6 family members. Results ·High-throughput sequencing results showed that 2.5 kb fragment deletion existed in the chromosome X (chrX: 13 732 385?13 734 927) of the proband, which covered exon 4?6 of the transport protein particle complex subunit 2 (TRAPPC2) gene. The quantitative PCR results confirmed the proband and his male cousin carried the deficiency. The proband′s mother had a heterozygous deficiency, and the proband′s father, sister and the uncle with normal phenotypes all had normal copy numbers. Conclusion ·The fragment deletion of exon 4?6 of TRAPPC2 gene is the pathogenic mutation of SEDT, and the XHMM algorithm in high-throughput sequencing analysis can detect the deletion of multiple exons in pathogenic genes.

Key words: spondyloepiphyseal dysplasia tarda (SEDT), high-throughput sequencing, transport protein particle complex subunit 2 (TRAPPC2) gene