Preonset studies of spondyloepiphyseal dysplasia tarda caused by a novel 2-base pair deletion in SEDL encoding sedlin

Spondyloepiphyseal dysplasia tarda (SEDT), an X-linked recessive skeletal d isorder, presents with disproportionate short stature and "barrel-chest" de formity in affected (hemizygous) adolescent boys. In four reported families to date, mutations in a gene designated SEDL (spondyloepiphyseal dysplasia late) cosegregate with SEDT. We diagnosed SEDT in a short-stature, kyphoti c 15-year-old boy because of his characteristic vertebral malformations. Cl inical manifestations of SEDT were evident in at least four previous genera tions. A novel 2-base pair (bp) deletion in exon 5 of SEDL was found in the propositus by polymerase chain reaction (PCR) amplification and sequencing of all four coding exons. The mutation ATdel241-242 cosegregated with the kindred's skeletal disease. The deletion is adjacent to a noncanonical spli ce site for exon 5 but does not alter splicing. Instead, it deletes 2 bp fr om the coding sequence, causing a frameshift. A maternal aunt and her three young sons were investigated subsequently. Radiographs showed subtle shapi ng abnormalities of her pelvis and knees, suggesting heterozygosity. X-rays of the spine and pelvis of her 8-year-old son revealed characteristic chan ges of SEDT, but her younger sons (aged 6 years and 3 years) showed no abno rmalities. SEDL analysis confirmed that she and only her eldest boy had the 2-bp deletion. Molecular testing of SEDL enables carrier detection and def initive diagnosis before clinical or radiographic expression of SEDT. Altho ugh there is no specific treatment for SEDT, preexpression molecular testin g of SEDL could be helpful if avoiding physical activities potentially inju rious to the spine and the joints proves beneficial.