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Missense and silent mutations in COL2A1 result in Stickler syndrome but via different molecular mechanisms
Author(s) -
Richards Allan J.,
Laidlaw Maureen,
Meredith Sarah P.,
Shankar Pallavi,
Poulson Arabella V.,
Scott John D.,
Snead Martin P.
Publication year - 2007
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9497
Subject(s) - missense mutation , genetics , biology , nonsense mutation , haploinsufficiency , mutation , rna splicing , glycine , exon , stop codon , frameshift mutation , gene , coding region , microbiology and biotechnology , amino acid , phenotype , rna
Stickler syndrome due to mutations in COL2A1 is usually the result of premature termination codons and nonsense mediated decay resulting in haploinsufficiency of type II collagen. Here we present two missense mutations and one apparently silent mutation that each result in Stickler syndrome, but via different molecular mechanisms. One alters the translation initiating ATG codon. The second mutation is a unique glycine substitution in the minor collagen helix of the procollagen. To our knowledge a glycine substitution has not previously been reported in this region of fibrillar procollagens. The third mutation appears to be a silent change altering a GGC codon to GGT both for glycine, but use of a splicing reporter assay demonstrates that it results in missplicing and a shift in the reading frame. © 2007 Wiley‐Liss, Inc.