PHENOTYPIC EXPRESSIONS OF A GLY154ARG MUTATION IN TYPE-II COLLAGEN IN2 UNRELATED PATIENTS WITH SPONDYLOEPIMETAPHYSEAL DYSPLASIA (SEMD)

Type II collagenopathies consist of chondrodysplasias ranging horn let hal to mild in severity. A large number of mutations has been found in the COL2A1 gene. Glycine substitutions have been the most common type s of mutation. Genotype-phenotype correlations in type II collagenopat hies have not been established, partly because of insufficient clinica l and radiographic description of the patients. We found a glycine-to- arginine substitution at position 154 in type II collagen in two unrel ated isolated propositi with spondylo-epimetaphyseal dysplasia and pro vide a comparative clinical and radiographic analysis hom birth to you ng adulthood for this condition. The clinical phenotype was disproport ionate short stature with varus/valgus deformities of the lower limbs requiring corrective osteotomies, and lumbar lordosis. The skeletal ra diographs showed an evolution from short tubular bones, delayed epiphy seal development, and mild vertebral involvement to severe metaphyseal dysplasia with dappling irregularities, and hip ''dysplasia.'' The me taphyseal abnormalities disappeared by adulthood. (C) 1996 Wiley-Liss, Inc.