STICKLER-LIKE SYNDROME DUE TO A DOMINANT-NEGATIVE MUTATION IN THE COL2A1 GENE

The type II collagenopathies include a wide spectrum of phenotypes ran ging from mild spondylo epiphyseal dysplasia (SED) to severe achondrog enesis/hypochondrogenesis. Several attempts have been made at providin g phenotype-genotype correlations in this group of disorders, In this report we discuss a South African family in which four members have a phenotype resembling Stickler syndrome type 1, Ocular problems and con ductive deafness predominate, while skeletal changes resemble those of a mild form of multiple epiphyseal dysplasia (MED), In distinction to the classical form of Stickler syndrome, the affected persons have st ubby digits. DNA analysis of the exons of the COL2A1 gene documented a C-T transversion in exon 39, resulting in an Arg704Cys substitution i n the triple helical domain of the type II collagen peptide; this nont ermination mutation may be indicative of further heterogeneity in the Stickler group of disorders or of a new syndrome amongst the type II c ollagenopathies, Am. J. Med, Genet, 80:6-11, 1998, (C) 1998 Wiley-Liss , Inc.