Mutation of acceptor splice site of the SEDL gene in X-linked spondyloepiphyseal dysplasia tarda causes the activation of cryptic splice site.

Objective: To further investigate the genetic basis of hereditary X-linked spondyloepiphyseal dysplasia tarda (SEDL) and provide useful information for the prevention and treatment of the disease.

Methods: RT-PCR and cDNA sequencing were used to test mRNA expression of SEDL gene in a patient with 13 bp deletion of SEDL gene involving the acceptor splice site of intron 5.

Results: Of two different sizes of mRNA products identified in the patient, the 393 bp product was created due to the activation of cryptic splice site within exon 6; the 433 bp product was completely consistent with the part of genomic sequence on chromosome 8.

Conclusion: The intragenic deletion that occurred in the acceptor splice site of the 3'region of intron 5 and the 5' coding region of exon 6 results in the activation of a cryptic splice site within exon 6, which causes 47 bp deletion of the resulting mRNA followed by a frameshift that would add two missense amino acids and then be followed by a termination codon (D109-S123del; S124fsX126). In addition, the mutation may activate the transcription of pseudogene SEDLP2 on chromosome 8 to partly complement the function of SEDL protein.