Loss of the SEDL gene product (Sedlin) causes X-linked spondyloepiphyseal dysplasia tarda: Identification of a molecular defect in a Japanese family

A 23-year-old man. was diagnosed as having X-linked spondyloepiphyseal dysp lasia tarda (SEDT; MIM 313400) based on his disproportionately short trunk, short stature, characteristic radiological features of the spine (posterio r hump, end plate sclerosis, and disc space narrowing) and the hips (short and thick femoral necks), and positive family history. This Japanese family was found to have an intragenic deletion flanking intron 2 and exon 3 of t he SEDL gene that not only included the 5' untranslated region but also the coding sequence for the first methionine through the 25th alanine. This mu tation was present in the proband and his unaffected mother (a heterozygote ), but not in an unaffected sister and an unaffected uncle. The nature of t he mutation predicted that the SEDL protein (Sedlin) was not produced in th e proband, indicating that loss of Sedlin caused SEDT (C) 2001 Wiley-Liss, Inc.