A novel mutation substituting tryptophan with arginine in the carboxyl-terminal, non-collagenous domain of collagen X in a case of Schmid metaphyseal chondrodysplasia

• Published in: Biochemical and biophysical research communications Vol. 217; no. 3; pp. 1157 - 1162
• Main Authors: Pokharel, R K, Alimsardjono, H, Uno, K, Fujii, S, Shiba, R, Matsuo, M
• Format: Journal Article
• Language: English
• Published: United States 26.12.1995
• Subjects: Amino Acid Sequence; Arginine; Base Sequence; Child, Preschool; Collagen - genetics; Exostoses, Multiple Hereditary - genetics; Female; Humans; Male; Molecular Sequence Data; Pedigree; Point Mutation; Tryptophan
• ISSN: 0006-291X

A novel nucleotide change in the collagen X gene was identified in a Japanese family with Schmid metaphyseal chondrodysplasia (SMCD). The T to C change at nucleotide 1951 resulted in replacement of tryptophan by arginine at residue 651 (W651R). This missense mutation is considered to be responsible for SMCD because 1, the same mutation was not be identified in the collagen X gene from normal individuals; 2, the mutation segregated with the SMCD phenotype in the index family; 3, the substituted amino acid is highly conserved in type X collagens, and 4, the mutation causes a marked change in the hydrophobicity profile of the surrounding region in the NC1 domain. This novel mutation (W651) seems to have the same impact on bone development as W651X mutation.