EHLERS-DANLOS SYNDROME TYPE-IV CAUSED BY GLY400GLU, GLY595CYS AND GLY1003ASP SUBSTITUTIONS IN COLLAGEN-III - CLINICAL-FEATURES, BIOCHEMICALSCREENING, AND MOLECULAR CONFIRMATION

Three patients with Ehlers-Danlos syndrome type IV (EDS IV) and bioche mical evidence of structural defects in collagen III were investigated for mutations within the collagen III gene (COL3Al). Single strand co nformation polymorphism analysis of alpha 1(III) cDNA indicated the pr esence of different heterozygous sequence changes in each of the patie nts. Nucleotide sequencing revealed mutations leading to the substitut ion of glycine 400 with glutamic acid, glycine 595 with cysteine, and glycine 1003 with aspartic acid. EDS IV is a life-threatening disorder which, as the clinical histories of our patients and their families s how, still often escapes diagnosis. Biochemical and molecular studies can clarify the diagnosis and help provide appropriate management and counselling.