Single-strand conformation polymorphism (SSCP) analysis of the COL3A1 gene detects a mutation that results in the substitution of glycine 1009 to valine and causes severe Ehlers-Danlos syndrome type IV

A single base mismatch was detected by single‐strand conformation polymorphism (SSCP) of the collagen type III gene in a patient with Ehlers‐Danlos syndrome type IV. The patient's fibroblasts secreted both normal and slowly migrating type III procollagen molecules. Two‐dimensional CNBr peptide mapping suggested that the defect was localised in the CB9 peptide or the C‐propeptide region of the α1(III)‐chain. Analysis of a set of restriction‐endonuclease‐digested fragments of an amplified cDNA sequence encoding CB9, identified a single‐strand conformation polymorphism and localized it within a region of 79 bp corresponding to the carboxyl‐terminal end of the CB9 peptide of the α1(III)‐chain. DNA sequence analysis demonstrated that the patient was heterozygous for a point mutation converting G to T at base pair 3440 of the collagen α1,(III) cDNA resulting in the substitution of glycine with valine at amino acid position 1009 of the α1(III)‐chain. The mutation in this patient lies within a region of mutations at the carboxyl‐terminal end of the type III collagen α‐helix which all produce a severe “acrogeric” form of EDS IV. © 1994 Wiley‐Liss, Inc.