Identification of three novel SEDL mutations, including mutation in the rare, non-canonical splice site of exon 4.

Spondyloepiphyseal dysplasia tarda (SEDT) is an X-linked recessive disorder, characterized by disproportionately short stature and degenerative joint disease, which manifests in the early teens. The gene responsible for SED tarda, SEDL, has been identified in Xp22. We report on three novel SEDL mutations. The first mutation is in the rare, non-canonical 5' splice site of intron 4 (IVS4+4T>C) in an Italian family. Reverse transcription-polymerase chain reaction (RT-PCR) analysis has revealed that this mutation causes alternative splicing of exon 5, and, as a consequence, inclusion of exon 4b sequence. This gives rise to an altered, truncated SEDL protein. We also describe two new deletions: one is a 4-bp deletion in exon 6 [333-336del(GAAT)], identified in a Slovak patient with SEDT, and one is a 1.335-kb deletion (in5/ex6del), found in a Belgian patient. The identification of these novel mutations in SEDL adds to the spectrum of 30 mutations previously identified. A short summary of all currently known SEDL gene mutations is presented.