OBJECTIVE: To investigate mutation of COL1A1 gene and analyze the relationship 
between genotype and clinical phenotype in a family with osteogenesis imperfecta 
(OI).
METHODS: The family history of an OI pedigree, along with clinical data, was 
collected. Blood samples from the proband and his families, as well as 50 normal 
controls, were collected. Mutation of COL1A1 gene was screened using PCR-high 
resolution melting (PCR-HRM) and validated by sequencing.
RESULTS: PCR HRM method showed an abnormal result in proband COL1A133_34 exons, 
which Tm was 87.7℃, in contrast to the normal control (wt) Tm of 87.9±0.06℃. 
There was a significant difference between the proband and the normal control 
with the standardization curve and the difference curves. DNA sequencing showed 
that Y9COL1A1 gene exons 33_34 has lost a C base (c.2321delC), which resulted in 
a frameshift mutation and caused an premature termination codon (UAA) at amino 
acid 334, i.e., p.Pro774LeufsX334 The father and grandfather of the proband, 
both suffered from OI, were verified to be heterozygous for the same mutation. 
The same mutation was not found in 50 normal controls. Database search confirmed 
this to be a novel mutation. Pedigree analysis suggested that it has an 
autosomal dominant inheritance. The proband and patients from the family were 
clinically diagnosed as OI type I.
CONCLUSION: The study has identified a novel mutation of COL1A1 gene, 
c.2321delC. This frameshift mutation has caused a premature stop codon and 
reduced collagen type synthesis, characterized by a lighter OI clinical 
phenotype.