Five Families with Arginine519-Cysteine Mutation in COL2A1: Evidence for Three Distinct Founders

Jane F. Bleasel1, Daniel Holderbaum2, Valeria Brancolini3, Roland W. Moskowitz2, Eileen L. Considine2, Darwin J. Prockop4, Marcella Devoto3,5, Charlene J. Williams4

1Department of Experimental Medicine, Centenary Institute of Cancer Medicine and Cell Biology, Sydney, NSW 2042, Australia
2Department of Medicine, Division of Rheumatic Diseases, Case Western Reserve University, Cleveland, Ohio 44106
3Laboratory of Statistical Genetics, Rockefeller University, New York, New York 10021
4Department of Biochemistry and Molecular Biology, Jefferson Institute of Molecular Medicine, Jefferson Medical College, Philadelphia, Pennsylvania 19107; Fax: 215-923-4649
5Laboratory of Molecular Genetics, Instituto G. Gaslini 16148, Genoa, Italy

Human Mutation, 12:172-176 (1998)

Abstract

Arginine519-cysteine mutation in the type II procollagen gene (COL2A1) is known to be associated with mild spondyloepiphyseal dysplasia (SED) and precocious generalized osteoarthritis (OA). Five families have now been identified with this mutation. To determine whether a common founder was responsible for the mutation in these five families, we defined the haplotype of the mutation-bearing chromosome using four restriction fragment length polymorphisms (RFLPs) and the 3'-untranslated region VNTR. Haplotype frequencies were estimated for 69 control samples. Three distinct mutation-bearing haplotypes were identified, with three families sharing a common haplotype. For three distinct haplotypes to have derived from a single founder, three independent recombination events would have had to occur. Thus the arg519 codon appears to represent a possible site of recurrent mutations in COL2A1, an uncommon phenomenon in collagen genes.